This study examined exercise-induced hypoxaemia (EIH) and plasma volume contraction as modulators of serum erythropoietin (Epo) production. Five athletes cycled for 3 min at supra-maximal power outputs, at each of two different elevations (1000 m and 2100 m). Five subjects were exposed to normobaric hypoxia ( F I O 2 = 0.159), seven subjects underwent plasmapheresis to reduce plasma volume and eight subjects were time controls for Epo levels. Oxyhaemoglobin saturation was significantly reduced during exercise and during normobaric hypoxia. The time period of haemoglobin oxygen saturation < 91% was 24±29 s (mean±S.D., n = 5) for exercise at 1000 m, 136±77 s (mean±S.D., n = 5) for exercise at 2100 m and 178±255 s (mean±S.D., n = 5) with resting hypoxic exposure. However, significantly increased serum Epo levels were observed only following exercise (24±3%; mean±S.D., n = 5 at 1000 m and 36±5%; mean±S.D., n = 5 at 2100 m). Volume contraction also resulted in increased serum Epo (35±6%; mean±S.D., n = 7) in spite of a significant rise in haematocrit of 2.2%. Despite similar degrees of arterial desaturation, only the hypoxaemia induced by exercise was associated with an increase in serum Epo. This finding indicates that other factors, in addition to hypoxaemia, are important in modulating the production of Epo in response to exercise. Volume depletion in the absence of exercise resulted in increases in Epo levels that were comparable with those observed in response to exercise. The paradoxical responses of the increased haematocrit and the increase in Epo in subjects undergoing plasmapheresis suggests that plasma volume may also modulate the production of Epo.

1. Studies were carried out on 43 otherwise healthy patients referred for investigation for attacks of syncope of unknown cause and on six healthy volunteers. 2. Plasma volume was determined by Evans Blue dye dilution and blood volume was estimated using haematocrit. Carotid baroreceptor sensitivity was determined from the changes in pulse interval in response to subatmospheric pressures applied to the neck overlying the carotid sinuses, and orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilt, followed by the addition of graded lower body suction. 3. Eight patients and one volunteer fainted during head-up tilt alone, 23 patients and two volunteers fainted during tilt with lower body suction at −20 mmHg and 12 patients and three volunteers either fainted during suction at −40 mmHg or tolerated the entire procedure. 4. Although plasma and blood volumes were higher in males than females, the values normalized for either body weight or for calculated lean body mass were not different between male and female patients and asymptomatic volunteers. The subjects showing the greatest resistance to syncope were found to have significantly larger plasma and blood volumes ( P < 0.0001) and significantly smaller baroreceptor sensitivities ( P < 0.0002) than those who fainted earlier. 5. There was a highly significant positive correlation in all subjects between orthostatic tolerance (time to onset of syncope) and plasma and blood volumes ( r = 0.60, P < 0.0001; r = 0.53, P < 0.0002), and highly significant negative correlations between time to syncope and baroreceptor sensitivity ( r = −0.61, P < 0.0001) and between baroreceptor sensitivity and plasma and blood volumes ( r = −0.54, P < 0.0001; r = −0.31, P < 0.03). 6. These results show that tolerance to orthostatic stress is favoured by large plasma and blood volumes and a low sensitivity of the carotid baroreceptor—heart rate reflex.

1. Iron absorption has been quantitatively measured as the incorporation of physiological doses of stable iron isotopes into erythrocytes. Five milligrams of 57 Fe (orally) and 250 μg of 58 Fe (intravenously) were given to five healthy women on 2 consecutive days. Fourteen days later the changes in the 57 Fe/ 56 Fe and 58 Fe/ 56 Fe ratios in the erythrocytes of each subject were measured using an inductively coupled plasma mass spectrometer. Isotope ratios were also measured in two subjects who were not given any enriched isotope. Concomitant measurements of plasma volume using a dye-dilution technique enabled the estimation of body iron mass and the calculation of iron absorption. 2. The mean coefficients of variation for the 57 Fe/ 56 Fe ratio and the 58 Fe/ 56 Fe ratio were 0.22% and 0.47%, respectively. This precision allowed enrichments of basal ratios to be reliably detected in all cases. The mean change in the 57 Fe/ 56 Fe ratio was 0.00116 ( sd 0.00052, P <0.001) and the mean change in the 58 Fe/ 56 Fe ratio was 0.00035 ( sd 0.00004, P <0.001). Control subjects showed no enrichment. 3. The calculated iron absorption ranged from 10% to 34%, and the amount of absorption was related to the iron stores of the subjects. Percentage iron absorption was identical when estimates of the plasma volume (derived from a body mass equation) were used instead of the plasma volume determined by dye-dilution measurements. Incorporation of intravenous iron into erythrocytes was on average 81% (range 68–93%). 4. The method is especially applicable to the study of iron absorption during pregnancy when incorporation into erythrocytes cannot be predicted.

1. Determination of the plasma volume in pregnant women is a useful research tool and may become an important clinical measurement. We used three methods to determine plasma volume using Evans Blue dye: (1) the ‘usual’ method, measuring serum absorbance at a wavelength of 610 nm, (2) a two-wavelength method, and (3) precipitation of non-albumin proteins by the addition of polyethyleneglycol before measuring serum absorbance at a wavelength of 620 nm. These were each compared with the standard 125 I-human serum albumin method in 20 non-pregnant subjects. Subsequently, the polyethylene glycol method was considered the standard and the three Evans Blue dye methods were compared in 20 pregnant women. 2. In non-pregnant subjects mean plasma volumes did not differ significantly according to the method used. However, the limits of agreement with 125 I-human serum albumin method were closest for the polyethyleneglycol method, for both clear and turbid sera. 3. In pregnant women, mean plasma volume values did not differ according to the Evans Blue dye method used, but the limits of agreement were significantly closer with the two-wavelength method than with the ‘usual’ method ( P <0.05) largely owing to the effects of turbid sera. 4. These studies demonstrate that considerable error may occur when the Evans Blue dye concentration is determined in turbid sera by the ‘usual’ method. This can be overcome by the use of the two-wavelength method or the polyethyleneglycol method. The most accurate results will be obtained if the latter method is employed routinely to determine plasma volume in pregnant women.

1. Capillary permeability was determined by the disappearance rate of Evans Blue dye from plasma in healthy non-pregnant women, normal third-trimester primigravidae and primigravidae with pregnancy-induced hypertension 2. Extracellular fluid volume was determined from the disappearance curves of injected mannitol in the same subjects and the plasma volume was measured by the Evans Blue dye dilution technique 3. In normal pregnancy capillary permeability was not altered from that of non-pregnant subjects. Although extracellular fluid volume and plasma volume were increased in normal pregnant compared with nonpregnant women, the distribution of fluid between plasma volume and interstitial fluid volume was unaltered 4. Women with established pregnancy-induced hypertension had a more rapid Evans Blue disappearance rate and a lower plasma volume than normal pregnant women, independent of the presence of proteinuria. Maternal plasma volume correlated positively and significantly with fetal birth weight in women with pregnancy-induced hypertension, emphasizing the important relationship between maternal plasma volume and fetal outcome 5. The increased capillary permeability in women with pregnancy-induced hypertension was associated with a reduction in the plasma volume/interstitial fluid volume ratio but a normal extracellular fluid volume, suggesting that the reduced plasma volume did not result from sodium loss but rather from a redistribution of the total extracellular fluid volume. These changes did not differ significantly in subgroups with and without oedema.

1. The effect of intravenous catecholamine infusions and of intravenous insulin on plasma volume and intravascular mass of albumin was investigated in healthy males. 2. Physiological doses of adrenaline (0.5 μg/min and 3 μg/min) increased peripheral venous packed cell volume significantly; intravenous noradrenaline at 0.5 μg/min had no effect on packed cell volume, whereas packed cell volume increased significantly at 3 μg of noradrenaline/min. No significant change in packed cell volume was found during saline infusion. 3. During adrenaline infusion at 6 μg/min, packed cell volume increased, plasma volume decreased and intravascular mass of albumin decreased significantly. During noradrenaline infusion at 6 μg/min, packed cell volume increased and plasma volume decreased, but intravascular mass of albumin did not change. 4. Application of a hyperinsulinaemic, euglycaemic glucose clamp led to an increase in transcapillary escape rate of albumin and a decrease in intravascular mass of albumin. Packed cell volume remained constant, while plasma volume, measured by radiolabeled albumin, decreased. 5. We conclude that the previously reported changes in packed cell volume, plasma volume, intravascular mass of albumin and transcapillary escape rate of albumin during hypoglycaemia may be explained by the combined actions of adrenaline and insulin.

1. The effect on fluid homoeostasis of walking 37 km on each of 4 consecutive relatively cool days was studied in six male subjects. The daily exercise intensity was consistent and was equivalent to 17(1)% [mean ( se )] of maximum oxygen uptake for these subjects. 2. The diet during the study consisted of a mainly carbohydrate breakfast, consumed immediately before each day‘s exercise, and unrestricted access to a normal mixed diet after completion of each day's exercise. Water was allowed ad libitum during the walk. Food and fluid intake were recorded. 3. Body weight remained constant over the 4-day walk. The difference between total daily fluid intake and the corresponding 24 h urine output was 1684 (250) ml, 1621 (522) ml, 1107 (252) ml and 1406 (208) ml, respectively, on each of the 4 exercise days. 4. There was a calculated increase of 21.3(6.6)% in plasma volume over the 4-day walk; the largest daily change [11.3(2.9)%] occurred during the walk on day 1. The increase in plasma volume was maintained for at least 4 days after completion of the walk. 5. From day 2, serum sodium concentration tended to increase during the exercise period and fell to the pre-exercise concentration during the overnight rest periods. The concentration of the other measured serum constituents remained relatively constant, and serum osmolality did not alter over the study period.

1. Hypoglycaemia was induced by insulin injected intravenously (0.15 i.u./kg body weight) in seven healthy young males. 2. Plasma volume was measured before and during hypoglycaemia by intravenous injection of 125 I before hypoglycaemia and of 131 I during hypoglycaemia. Plasma volume decreased and transcapillary escape rate increased significantly during hypoglycaemia. 3. Skin temperature and local subcutaneous adipose tissue blood flow were measured in four different regions. Both tended to decrease during hypoglycaemia and decreased significantly 2 h after hypoglycaemia. There was no correlation between changes in the two measurements, suggesting that there is no simple relationship between subcutaneous blood flow and skin temperature during hypoglycaemia.

1. The effects of a 48 h infusion of arginine vasopressin (AVP) were measured in five separate studies on four normal salt-restricted physicians, in whom fluid retention was prevented. 2. The infusion was associated with an increase in renal sodium excretion which continued during the 24 h after the infusion had been discontinuted. 3. During the infusion plasma renin activity (PRA), plasma aldosterone and noradrenaline, and packed cell volume (PCV) fell; glomerular filtration rate, assessed by endogenous creatinine clearance, increased. 4. The findings are best explained by a vasopressin-induced increase in plasma volume, which in the absence of fluid retention is likely to have been due to a redistribution of body water.

1. Adrenal regeneration hypertension was induced in male Wistar rats by unilateral adrenal enucleation, contralateral adrenalectomy and the provision of a 1% (w/v) NaCl solution for drinking. 2. A fivefold increase in dietary KCl content caused a significant reduction in the systolic blood pressure of hypertensive rats but not of control rats. 3. During the increase in potassium intake there was a marked polydipsia. When 1% NaCl solution was the drinking fluid, the resultant increase in sodium intake was associated with an abolition of the antihypertensive effect of potassium loading, but when the sodium intake was held constant, the antihypertensive effect was maintained. 4. In rats with adrenal regeneration hypertension, plasma volume was significantly higher, and packed cell volume and plasma protein concentrations were significantly lower than in control rats. These differences were abolished after 4 days of dietary KCl supplementation. 5. Increased dietary potassium intake was associated with significantly lower serum aldosterone concentrations and significantly higher plasma potassium concentrations in adrenal enucleated rats compared with controls. 6. The possibility that a reduction in extracellular fluid volume (due to a natriuresis) and/or a peripheral vasodilatation contributed to the antihypertensive effect of KCl loading is discussed.

1. We studied 12 normotensive non-ketotic diabetic patients during poor metabolic control, with sustained hyperglycaemia, and again, after an interval of 3 weeks, when metabolic control was improved. On each occasion we measured blood pressure, total exchangeable sodium, plasma volume, transcapillary escape rate of albumin, and plasma concentrations of angiotensin II and aldosterone. 2. With improved diabetic control there was a small but significant fall in arterial pressure. Total exchangeable sodium was normal when control was poor but rose significantly to above normal with improved control. 3. Plasma volume also rose significantly with improved control, and the transcapillary escape rate of albumin fell and the intravascular mass of albumin rose. 4. Plasma angiotensin II and aldosterone concentrations were significantly above normal during poor metabolic control, but fell to normal with improved control. 5. These findings indicate a resetting of the relationship between blood pressure and exchangeable sodium when diabetic control improves. The association between exchangeable sodium and concentrations of angiotensin II and aldosterone also appears altered in diabetic patients. These changes associated with varying metabolic control must be considered when studying cardiovascular disease in diabetic patients.

1. The effect of 5 consecutive days of hill walking on electrolyte balance, fluid homeostasis, plasma renin activity and plasma aldosterone concentration was studied in five male subjects. 2. The 5-day exercise period was preceded by a 4-day control period and followed by a 4-day recovery period. Throughout the 13-day study subjects ate a fixed diet. 3. After 5 days of exercise subjects had retained a mean of 264 mmol (sd 85) of sodium. Plasma sodium concentration remained constant at 142.0 mmol/l (sd 5.4). This indicates an expansion of the extracellular space by 1.84 litres. 4. By the end of the exercise period there was a positive water balance of about 0.9 litre. Thus there was a net movement of 0.94 litre of fluid from the intracellular to the extracellular space. 5. Packed cell volume decreased from a mean of 43.5% to 37.9% after 5 days of exercise, indicating that about 0.9 litre of the extracellular fluid entered the vascular compartment. The remaining fluid may be responsible for the significant increase in lower leg volume. 6. During the exercise period plasma aldosterone concentration and plasma renin activity rose, and there was a highly significant correlation between these values and the sodium retention. There was also a significant correlation between sodium retention and the increase in leg volume, which suggests that oedema may be the result of prolonged exercise of this type.

1. Erythrocyte mass, plasma volume (PV), extracellular fluid volume (ECFV) and total body water were simultaneously measured in 30 normotensive and 30 normal-renin hypertensive Caucasian male subjects for accurate determination of the presence or absence of a disorder(s) in body-fluid composition in hypertension. 2. The results indicate that plasma volume and total blood volume are lower in hypertensive subjects than in normotensive control subjects. The PV comprised 19% of the ECFV in both control and hypertensive subjects. 3. ECFV was lower in hypertensive subjects than in normotensive control subjects; the PV and interstitial fluid components of the ECFV were reduced by similar proportions. The ECFV, furthermore, comprised a smaller portion of the total body water in hypertensive subjects than that in control subjects. 4. We conclude that in the hypertensive state there is a reduction in the ECFV, but that there is no change in the partition of the ECFV between the plasma and interstitial components.

1. Plasma and interstitial fluid volumes have been measured simultaneously in men with uncomplicated and untreated essential hypertension. 2. Plasma volume (Evans blue) was reduced in essential hypertension and correlated inversely with blood pressure. 3. Interstitial fluid volume, derived from bromine space and plasma volume, was also reduced in essential hypertension and correlated inversely with blood pressure. The mean reduction in both plasma and interstitial fluid volumes was 6–7%. 4. There is no evidence for volume expansion in essential hypertension and the relationship between plasma and interstitial fluid volumes is preserved. The contraction of plasma and interstitial fluid volumes is most likely to reflect a natriuresis and diuresis secondary to the raised renal perfusion pressure, and sodium retention is unlikely to be a primary event in essential hypertension.

1. We have investigated left ventricular function in 25 selected patients with chronic bronchitis by use of atrial pacing and plasma volume expansion. Nine subjects had a past history of acute respiratory failure. None had either clinical or electrocardiographic signs of coronary heart disease. Paradoxical pulse was absent, since the difference between the highest and lowest systolic arterial pressure throughout the respiratory cycle was 5.4 ± 1.5 mmHg. 2. During atrial pacing, at a mean rate of 145 ±15, about 80% of the predicted maximal rate, none of the patients showed anginal pain or ventricular repolarization abnormality. Cardiac output remained unchanged compared with control values. 3. Plasma volume expansion was achieved by intravenous injection of 1 litre of gelatin over 30 min. Cardiac output, pulmonary wedge pressure and right atrial pressure rose as reported in literature for normal subjects. In four patients cardiac output did not increase although wedge pressure and right atrial pressure did; two of these four patients also had an overshoot in pulmonary wedge pressure just after atrial pacing, suggesting left ventricular dysfunction. Three out of 25 patients had high control right atrial pressures, probably in relation to impaired right ventricular function. No paradoxical pulse occurred during plasma volume expansion. Therefore competition for space in the pericardium between ventricles was unlikely. 4. Our data suggest that left ventricular dysfunction is rare in patients with chronic obstructuve pulmonary disease. There was no significant difference between subjects with and without a past history of acute respiratory failure.

1. Repeated measurements of blood pressure, cardiac output ( 99m Tc-labelled albumin dilution with single-probe precordial counting of radioactivity), plasma volume and extracellular volume were made in 20 subjects exposed to mineralocorticoid excess. Patients with aldosterone-producing adenoma ( n = 14) were followed for 6 weeks during the recurrence of hypertension after spironolactone treatment had been stopped. Patients with adrenal insufficiency ( n = 4) were followed for 6–9 weeks after treatment with dexamethasone (1 mg daily) and fludrocortisone (0.5 mg daily) was begun. Patients with severe orthostatic hypotension due to autonomic insufficiency ( n = 2) were followed for 21 and 120 weeks while treated with fludrocortisone (0.25 mg daily). Measurements were made weekly during the first 6 weeks and with longer intervals thereafter. 2. All subjects showed increments of cardiac output, stroke volume, plasma volume and extracellular volume during the first 2 weeks with little or no increase in total peripheral resistance. Mean blood pressure rose from 104 ± 3 to 126 ± 5 mmHg (mean ± sem ) ( P < 0.001, n = 14) in that period in primary aldosteronism and from 85 ± 4 to 94 ± 6 mmHg ( P > 0.05, n = 6) with fludrocortisone. 3. After 6 weeks hypertension was maintained by increased resistance in nine subjects, whereas cardiac output and plasma volume had returned towards normal (mean blood pressure at the end of the study 127 ± 4 mmHg). In the remainder hypertension was maintained by increased cardiac output and expanded plasma Volume for at least 6 weeks (mean blood pressure at the end of the study 131 ± 8 mmHg). The patients with the high-resistance pattern were older (56 ± 2 years) than the patients with the high-flow pattern (34 ± 2 years) ( P < 0.01). 4. Mean blood pressure and extracellular fluid volume were positively correlated ( r = 0.63, P < 0.001, n = 161). Cardiac output was positively correlated with plasma volume ( r = 0.51, P < 0.001, n = 161), and total peripheral resistance was inversely correlated with the plasma volume/interstitial fluid volume ratio ( r = 0.47, P < 0.001, n = 161). 5. The long duration of a high-flow state and the interindividual differences in progression of high-resistance hypertension argue against a cause-and-effect relation between flow and resistance through local metabolic factors (auto-regulation) as a hypertensive mechanism in sodium loading. The results are compatible with the view that fluid-shifts between the intravascular and extravascular compartments can influence the changes in cardiac output and resistance in early and sustained hypertension due to sodium overload. Cardiac output is increased when the proportion of fluid that is retained in the intravascular compartment is relatively high, and vascular resistance is increased when that proportion is relatively low.

1. The antihypertensive effect of 4 weeks' treatment with prizidilol (SKF 92657) (mean dosage 520 mg once or twice daily) was studied in ten essential hypertensive patients. 2. Both systolic and diastolic blood pressure were significantly reduced in all cases. Supine heart rate did not change, and in the erect position heart rate was significantly lowered. 3. Blood pressure reduction was due to peripheral vasodilatation, as the cardiac index increased after 4 weeks of prizidilol treatment. 4. After prizidilol plasma noradrenaline and adrenaline increased significantly, and PRA and plasma aldosterone were reduced. Although plasma volume increased, body weight did not change. 5. Cardiac performance, as evaluated by the PEP/LVET ratio, improved after treatment with prizidilol.

1. The haemodynamic and plasma volume changes associated with obesity and high blood pressure were studied in nine male rats with electrolytic ventromedial hypothalamic lesions and their paired sham-operated controls. Body weight and arterial pressure were greater in the rats with ventromedial hypothalamic lesions (565 ± 16 vs 462 ± 14 g, P <0.001; 128 ± 3 vs 118 ± 3 mmHg, P <0.05, respectively). Cardiac output was slightly elevated, and that portion of cardiac output distributed to the kidneys was reduced ( P <0.001). Plasma volume was contracted in the rats with ventromedial hypothalamic lesions (21.0 ± 0.1 vs 2.8 ± 0.1 ml/100 g, P <0.001). 2. The haemodynamic characteristics of rats in which obesity and mild hypertension have been induced by electrolytic ventromedial hypothalamic lesion are similar to mild obesity essential hypertension in men.

1. The effect of acute hypercalcaemia on blood pressure, blood volume, haemodynamic indices, plasma catecholamines, renin and aldosterone levels was investigated in 10 patients. 2. Calcium infusion (15 mg/kg over 3 h) increased ( P <0.05) plasma calcium and adrenaline levels, blood pressure, total peripheral resistance and packed cell volume. Plasma volume was decreased, and heart rate, cardiac output and plasma renin, aldosterone or dopamine levels were not significantly changed. Plasma noradrenaline was increased only minimally after 3 h of calcium infusion. 3. Mean blood pressure before and during calcium infusion correlated with concomitant serum calcium ( r = 0.39; P <0.02) or adrenaline levels ( r = 0.57; P <0.01); changes in blood pressure correlated with variations in plasma adrenaline ( r = 0.68; P <0.001). 4. Acute hypercalcaemic hypertension is mediated by an increase in peripheral vascular resistance and may be induced by a direct effect of calcium on blood vessels. The calcium-mediated increase in adrenaline release may play a contributory, and plasma volume contraction an inhibitory, role.

1. Salt loading accelerates and increases the rise in blood pressure (spSH) in stroke-prone spontaneously hypertensive rats, but not in Wistar-Kyoto (WK) rats. 2. In both strains a slight increase in plasma volume was obtained during salt loading. 3. Salt loading caused a distinct increase in plasma noradrenaline concentration in spSH rats, but a slight decrease in WK rats. Plasma adrenaline and dopamine concentrations remained unaffected. 4. Exposure to cold resulted in a more marked stimulation of sympathoadrenal and sympathoneuronal activity in salt-loaded spSH rats than in spSH rats on a normal sodium diet. 5. It is concluded that salt loading results in a further increase of the already elevated sympathetic activity in spSH rats.

1. Renal blood flow, glomerular filtration rate, renal vascular resistance and filtration fraction were studied in ten patients with essential hypertension, during placebo, and after 1 week, 3, 6 and 9 months of hydrochlorothiazide. Plasma renin concentration and urinary excretion of vanillylmandelic acid were also measured. 2. Mean arterial pressure was lowered significantly during hydrochlorothiazide, the long-term effect being slightly more pronounced than the short-term effect. 3. The decrease in renal blood flow during the first week ( P < 0·01) was followed by a progressive rise. After 9 months renal blood flow was above placebo level in eight of the ten patients. After an initial decrease, glomerular filtration rate returned gradually to its original value. Renal vascular resistance and filtration fraction increased during the first week and declined thereafter. After 3, 6 and 9 months renal vascular resistance was significantly lower compared with placebo values. 4. Plasma renin concentration and urinary excretion of vanillylmandelic acid increased significantly during the first week of hydrochlorothiazide. Subsequently, vanillylmandelic acid fell to below pretreatment amounts ( P < 0·05), whereas plasma renin concentration remained elevated. 5. Long-term treatment of essential hypertension with hydrochlorothiazide has a favourable effect on abnormal renal haemodynamics. Besides the influence of blood pressure reduction per se , humoral and neural factors may be involved.

1. Urinary kallikrein, renal tissue kininogenase activity, and plasma kininogen were measured during the development of hypertension in rats, either with left renal artery clamped and contralateral kidney intact (Goldblatt 2-kidney) or removed (Goldblatt 1-kidney). Plasma urea, plasma volume and blood volume were also measured. 2. In Goldblatt 2-kidney rats, urinary kallikrein was not significantly different from that of sham-operated rats up to the 5th post-operative week even though at this time the Goldblatt 2-kidney animals were hypertensive. Urinary kallikrein started to decrease at week 8. Plasma kininogen was significantly elevated 5 and 10 weeks after surgery and returned to normal by week 15. No changes in renal tissue kininogenase activity were observed. Plasma urea and plasma and blood volumes were normal 5 weeks after, but significantly increased at 10 and 15 weeks after surgery. 3. In Goldblatt 1-kidney rats from the fifth week urinary kallikrein and renal kininogenase activity were significantly decreased compared with unilaterally nephrectomized rats, whereas plasma kininogen, plasma urea and plasma and blood volumes were significantly elevated. 4. These results show important differences in the kallikrein system between the Goldblatt 1-kidney and 2-kidney models of renovascular hypertension in rats.

1. Six patients with borderline hypertension underwent training in exteroceptive biofeedback (BFB) in order to increase or decrease arterial pressure. 2. Systemic haemodynamics, intravascular volume and peripheral renin activity were determined before, during and after training sessions. 3. BFB training resulted in a significant reduction in mean arterial pressure (from 116 ± 4·6 to 101 ± 2·5 mmHg) mediated through a fall in total peripheral resistance; cardiac output, heart rate, intravascular volume and plasma renin activity remained unchanged. 4. In contrast, the increase or decrease of arterial pressure that occurred during BFB training was produced predominantly through changes in cardiac output and heart rate respectively, whereas total peripheral resistance under these circumstances remained unaffected. 5. The haemodynamic effects of BFB seem remarkably similar to the immediate or chronic effects of β-adrenoreceptor blockade, initially producing a fall in cardiac output followed by a reduced arterial pressure associated with a decreased total peripheral resistance.

1. Blood pressure, systemic haemodynamics, plasma volume, renin and aldosterone were measured during placebo treatment and after 1, 4 and 12 weeks of hydrochlorothiazide in 13 patients with uncomplicated essential hypertension. Nine of these patients were also studied after 24 and 36 weeks of treatment. 2. Mean arterial pressure was lowered significantly during hydrochlorothiazide treatment. In seven patients the fall in mean arterial pressure was greater than 10% (responders); four of these were studied for 36 weeks. The remainder were considered non-responders. 3. Hydrochlorothiazide lowered cardiac output. The maximal decrease was observed after 12 weeks of treatment ( P < 0·01). In responders this was followed by a return to pretreatment values and a significant decrease in total peripheral resistance, whereas in non-responders cardiac output remained reduced and total peripheral resistance was permanently elevated. 4. Changes in plasma volume, renin and aldosterone were not significantly different in responders and non-responders although non-responders tended to show a greater degree of plasma volume depletion and a more pronounced increase in plasma aldosterone. 5. Thus it is unlikely that the initial decrease in cardiac output is an important determinant of the long-term haemodynamic effect of thiazide diuretics.

1. Rats with indwelling aortic and right atrial cannulae were maintained on a sodium-free diet before and after renal arterial constriction combined with contralateral nephrectomy. Control animals underwent the same protocol except that non-constricting clips were used. 2. Plasma volumes in the salt-deprived animals were lower than previously determined values in animals with free access to sodium. After clipping plasma volume increased in the hypertensive animals. Extracellular fluid volume was increased equally in both normotensive and hypertensive animals on the second postoperative day only. 3. Before clipping and contralateral nephrectomy plasma angiotensin II values were higher than normal. After the operation angiotensin II concentrations fell to normal over a period of 14 days without significant differences between experimental and control groups. 4. It is concluded that high blood pressure after clipping may be in part maintained by increases in plasma volume. However, the results strongly suggest that other renal mechanisms are likely to be of major pathogenic importance.

1. The protective action of the renal medulla was studied in one-kidney renal-clip hypertension in rats with unilateral hereditary hydronephrosis and almost complete atrophy of the medulla of the affected kidney. 2. Rats were unilaterally nephrectomized. The first group had a normal kidney remaining, and the animals from the second and third groups were left with a hydronephrotic kidney and received renomedullary and renocortical autotransplants respectively. Two weeks later all rats were made hypertensive by placing a silver clip (0·2 mm) on the renal artery. 3. From the fourth day after clipping until the end of the experiment blood pressure was found to be significantly ( P < 0·01) lower in rats with medullary transplants than in the other groups. No differences in renal excretory function, plasma volume and plasma renin activity were found between the groups either before or during development of hypertension (5 and 21 days after clipping). Early in the course of hypertension (5 days) cardiac output was significantly ( P < 0·05) lower in the rats with medullary transplants than in the other groups, although an increase in plasma volume was noted in all three groups. At that time no difference in total peripheral resistance was found between the groups. 4. The results are consistent with the hypothesis that the renomedullary antihypertensive substance(s) mitigates hypertension by preventing a hypertensive haemodynamic response to sodium/volume overload.

1. The relationship of basal plasma noradrenaline to blood pressure, age, sex, urinary sodium excretion, and plasma volume has been examined in 117 untreated ambulatory patients with essential hypertension. 2. No significant correlations between basal plasma noradrenaline and either age or sex were apparent in the total group of essential hypertensive patients. In addition, no significant correlations were observed between plasma noradrenaline and 24 h urinary sodium excretion. 3. Basal plasma noradrenaline concentration was significantly higher in high renin essential hypertensive subjects compared with those with normal or low plasma renin activity. 4. Plasma noradrenaline was reduced significantly in relatively young patients with low renin essential hypertension, but appeared to be normal in other low renin subjects. 5. Basal plasma noradrenaline correlated significantly with blood pressure in patients with normal or low renin essential hypertension but the relationships were only significant in male patients. 6. No significant relationship between basal plasma noradrenaline and either blood pressure or plasma volume could be demonstrated in this population of essential hypertensive patients.

1. Almost all the factors that may cause a rise in blood pressure are, in turn, influenced by the increase in blood pressure per se. Thus any primary involvement of one or more of these factors in the pathogenesis of essential hypertension must be evaluated before or during the development of hypertension. 2. Young normotensive subjects both of whose parents are hypertensive have a much higher probability of developing hypertension than those whose parents are both normotensive. 3. The following measurements were made in 56 subjects of the first group (both parents hypertensive) and 35 of the second group (both parents normotensive), matched for age, sex and body surface area: renal plasma flow and glomerular filtration rate, using p -aminohippurate and inulin clearance; 24 h urinary excretion of aldosterone, protein and electrolytes; plasma renin activity; plasma volume. Plasma catecholamines and cardiac index were also measured in 26 subjects of the first group and 25 subjects of the second group using a radioenzymic method and echocardiography. 4. All these factors were similar in the two groups except that renal plasma flow was higher in the first group (767·2 ± 30 versus 650·7 ± 17 ml/min, P < 0·01). Plasma renin activity tended to be lower in subjects with a higher renal plasma flow, but there was no significant negative correlation between the two factors. 5. The possibility that the higher renal plasma flow in subjects with a high probability of developing hypertension is a compensatory mechanism for a primary intrarenal defect is discussed.

1. Twelve conscious, chronically instrumented dogs were subjected to rapid loading with sodium chloride solution (150 mmol/l; saline) before and 1 day after bilateral nephrectomy (six dogs) or uretero-caval anastomosis (six dogs). Measurements were performed up to 3 h after the fluid load and included cardiac output with an electromagnetic flowmeter, mean arterial pressure and right atrial pressure with chronically implanted catheters, interstitial fluid pressure with a plastic capsule, heart rate, extracellular fluid volume, erythrocyte volume, plasma volume, plasma protein concentration and other variables. 2. The increase in cardiac output in response to saline load was significantly prolonged in the anephric dogs compared with those with uretero-caval anastomosis; mean arterial pressure, right atrial pressure and heart-rate changes were similar in both groups. 3. Plasma volume appeared to increase more in the anephric dogs than in those with uretero-caval anastomosis during the first hour after the infusion, although conflicting results were obtained with different estimates of plasma volume changes. Interstitial fluid pressure increased significantly less in the anephric dogs in the early stages of the fluid load. 4. Effective vascular compliance (the ratio of the change in blood volume to the change in right atrial pressure) appeared increased in the anephric dogs. On the other hand, the change in cardiac output for a given change in right atrial pressure was found to increase after bilateral nephrectomy. 5. It is suggested that the prolonged increase in cardiac output observed in anephric dogs was not the consequence of preferential plasma volume expansion nor of decreased venous compliance, but may reflect an alteration in the cardiac function curve.

1. Fourteen mildly hydropenic normal volunteers were slowly tilted at a constant rate from the horizontal to the 85° head-up position in order to study the interrelationship between plasma arginine vasopressin concentration, plasma renin activity and the change of plasma volume. 2. Nine subjects did not develop vaso-vagal symptoms and were studied for 45–60 min. Arginine vasopressin rose biphasically in all subjects: a small initial rise, which was seen at 3 min and persisted for 30 min, was followed by a striking rise between 30 and 45 min, when the fall of plasma volume had reached its maximum (17%). 3. Plasma renin activity reached a maximum at 30 min but fell by 45 min, as plasma concentration of arginine vasopressin rose. 4. Five subjects developed vaso-vagal symptoms 4–24 min after reaching 85° when the study was terminated. A striking increase of arginine vasopressin concentration was seen within 4 min of syncope, but there was no change of plasma osmolality, cortisol concentration or renin activity.

1. The changes in plasma enteroglucagon concentration and plasma volume were measured after oral glucose in sixteen subjects before and forty-eight subjects after operative treatment for benign duodenal ulceration. Truncal vagotomy with a drainage procedure had been performed in sixteen of the postoperative subjects studied, selective vagotomy with a drainage procedure in seventeen, and partial gastrectomy in fifteen. 2. Patients in whom the glucose produced dumping symptoms had significantly greater enteroglucagon concentrations than those who were symptom-free, which confirms the results of a preliminary study. There was a highly significant correlation between the rate of rise of plasma enteroglucagon and the rate of fall of plasma volume. 3. There was no difference in the rate of rise or in peak plasma enteroglucagon concentration between the groups of patients who had different operative procedures. This suggests that enteroglucagon release is not under vagal influence. 4. There was no apparent relation between the plasma enteroglucagon concentration and the time-interval between the operation and the time of study, which implies that the exaggerated release of enteroglucagon after operation occurs in response to the altered gastric physiology and that there is minimal adaptive change.

1. Arginine vasopressin was infused into seven healthy young male volunteers at 12·5 and 25 units/min for 1 h at each dose. Plasma renin activity fell sharply and progressively in each subject. The mean fall was 47% and 66% of the initial value at the end of the lower and higher rates of arginine vasopressin infusion respectively; over 70% of the observed fall in plasma renin activity occurred at the end of the first infusion period. 2. The majority of the plasma arginine vasopressin concentrations achieved were within the physiological range observed after fluid deprivation and orthostatic stress in man, particularly at the lower rate of infusion. 3. There was no change of arterial pressure, despite a slight bradycardia at the lower rate of infusion; at the higher rate of infusion, there was only a very slight pressor response. 4. There was a concomitant and significant fall of plasma protein concentration and peripheral venous packed cell volume without any significant change of plasma sodium concentration or plasma osmolality, implying an expansion of plasma volume. 5. The results indicate that, in man, physiologically relevant amounts of arginine vasopressin suppress the rate of renin secretion indirectly by increasing the plasma volume at the expense of the extravascular fluid volume.

1. The cardio-renal haemodynamic and endocrine effects of the anti-hypertensive agents 2-(2,6-dichlorophenylamine)-2-imidazoline hydrochloride (clonidine, St 155) and 2-(5-fluor- o -toluidine)-2-imidazoline hydrochloride (St 600) were investigated in twelve patients with essential hypertension. 2. The anti-hypertensive action of both compounds was similar and was accompanied by a reduction in heart rate and in cardiac output, total peripheral resistance being unchanged. There was no alteration in renal blood flow and glomerular filtration rate, and renal vascular resistance showed a significant decrease. Blood volume and plasma renin concentration did not change significantly. An inverse relation between changes in plasma volume and plasma aldosterone concentration was observed. In the face of similar reductions in blood pressure, no differences were observed between systemic and renal haemodynamic and endocrine responses after clonidine and St 600.

1. As experimental models of reduced nephron population in man, (a) twelve men aged 15–32 years who had one kidney removed 1–13 years previously and (b) fourteen normotensive men aged 70–90 years were studied. Results were compared with those in eighteen normotensive men aged 18–28 years and eleven men aged 19–33 years with essential hypertension. 2. While the subjects followed a routine of normal diet and daily activity, measurements were made, after overnight recumbency and in the fasting state, of plasma volume and renin activity on one occasion in hospital and of blood pressure on five to fourteen occasions in the home. Blood pressure was also measured after standing for 2 min and plasma renin activity after 1 h standing, sitting or walking. Twenty-four hour urinary aldosterone excretion was also measured. 3. The measurements were repeated in the normotensive subjects and subjects in (a) and (b) above after 10 days of sodium-restricted diet (40 mmol of sodium/day). 4. The mean plasma renin activity (recumbent) in essential hypertensive subjects was higher than in normotensive subjects. In subjects of (a) and (b) above, it was lower than normotensive subjects, and was not increased by dietary sodium restriction in subjects of (a). 5. The mean aldosterone excretion level was lower in old normotensive subjects than in the other groups, and increased in each group after dietary sodium restriction. 6. Mean plasma volume/surface area was not different between the four groups and in normotensive, essential hypertensive and nephrectomized subjects but not subjects aged 70–90 years was negatively correlated with standing diastolic blood pressure.

1. The rate of renal excretion of arginine-vasopressin was determined during unrestricted fluid intake for 24 h and in response to fluid deprivation for 18 h in nine young men with very mild essential hypertension and compared with that in sixteen normotensive men of similar age. 2. Despite an equilavent osmolar stimulus, excretion of arginine-vasopressin was significantly greater in the hypertensive group than in the reference group. This difference increased progressively with increasing dehydration. 3. We suggest that these findings are mainly due to an increased rate of secretion of arginine-vasopressin in response to mild hydropenia in hypertensive patients and that a moderate increase of release of arginine-vasopressin during periods of fluid deprivation may exert vascular effects and thus influence the perpetuation of hypertension.

1. Water and electrolyte excretion was measured in the follicular and luteal phases of the menstrual cycle in seven patients with idiopathic oedema and in four post-menopausal patients with this condition. 2. In contrast to previous findings in healthy women, the reduction in urinary flow and sodium excretion on being tilted to the upright position was not significantly different in the follicular and luteal phases in pre-menopausal patients and there were no significant differences between pre- and post-menopausal patients. 3. The percentage increase in packed cell volume on standing was significantly greater in patients with idiopathic oedema than in normal subjects in the luteal phase of the menstrual cycle. 4. It is postulated that the enhanced retention of electrolytes and water in response to tilting in patients with idiopathic oedema is a compensatory mechanism for the decreased effective blood volume at that time.

1. 24 h aldosterone secretion rates (ASR) have been measured in six normal volunteers while recumbent all day and while standing for 12 h, on 200 and 10 mmol/day sodium diets and after salt-poor albumin infusions (75 g in 150 ml), which significantly expanded plasma volume. 2. The mean ASR on the 10 mmol/day sodium diet, both without and with the salt-poor albumin infusion, was highly significantly increased above the mean ASR on the 200 mmol/day sodium diet, both in the recumbent and in the upright posture. 3. There was no significant difference between the mean ASR values on the 10 mmol/day sodium diet alone and after the infusion of albumin either in the recumbent or in the upright posture. 4. The above observations suggest that sodium deprivation raises ASR by a mechanism or mechanisms unrelated to plasma volume.

1. To determine the part played by changes in interstitial tissue compliance in the mechanism of experimental renal hypertension, pressure and volume measurements were made in rats 60 days after partial constriction of one renal artery with a clip and removal of the opposite kidney. Tissue pressure and venous pressure were found to be significantly higher in rats which developed systolic arterial blood pressure of 140 mmHg or above than in loosely clipped controls with normal blood pressure. Plasma volume (PV) was also increased in the hypertensive animals, but there was no difference in interstitial fluid volume (IFV); the PV/IFV ratio was significantly higher in the hypertensive rats. 2. Removal of the clip in the hypertensive rats restored blood pressure to normal in 1 h; this was associated with a fall in venous pressure and plasma volume. Tissue pressure fell despite a rise in interstitial fluid volume; the PV/IFV ratio fell. 3. It is suggested that renal artery constriction, possibly by a humoral mechanism, causes a fall in interstitial space compliance and that this, by causing changes in body fluid distribution, plays a part in the mechanism of experimental renal hypertension. This mechanism may have a physiological role in the maintenance of adequate plasma volume during water shortage.

1. In nineteen patients, five with unilateral renal artery stenosis and fourteen with essential hypertension (WHO grades I–II), blood pressure, plasma and extracellular fluid volumes and plasma renin activity were studied at the end of three sequential periods: (a) after at least 3 days on a 60 mmol Na + diet; (b) after 3 days of salt depletion induced with a diuretic and sustained on a 20 mmol Na + diet; (c) after 3 days during which the 20 mmol Na + diet was continued and beta-receptor blockade was induced by increasing dosages of propranolol up to 320 mg daily. 2. After sodium depletion extracellular fluid volume and plasma volume decreased and plasma renin activity increased; blood pressure did not change significantly. 3. After adding propranolol, plasma volume and extracellular fluid volume remained low, and there was a significant decrease in plasma renin activity and blood pressure. 4. No correlation could be demonstrated between changes of blood pressure and plasma renin activity. 5. When the responses of the five patients with renal artery stenosis were compared with those of the fourteen patients with essential hypertension, no significant differences were found. 6. Propranolol has a strong anti-hypertensive effect after Na + depletion, irrespective of the absolute activities of plasma renin.

1. Haemodynamic studies were performed in six patients with hypertension, hyper-aldosteronism and low plasma renin (five patients with a solitary adrenocortical adenoma, one patient with bilateral adrenocortical nodular hyperplasia), and in ten normotensive control subjects. 2. Studies in the chronic phase of hypertension uniformly showed elevated total peripheral resistance while cardiac output was not increased. 3. In four patients haemodynamics were studied in the early phase of hypertension following a normotensive period induced by spironolactone. Under these latter conditions the raised blood pressure was associated with increased cardiac output whereas total peripheral resistance was normal. It is suggested that the haemodynamic pattern observed during the phase of the renewed elevation of blood pressure is similar to that at the onset of aldosterone-induced hypertension. 4. Serial measurements in two patients revealed that the haemodynamic characteristics were dependent on the phase of hypertension: during the chronic phase total peripheral resistance was increased whereas cardiac output was not. The new rise in blood pressure following discontinuation of spironolactone therapy was associated with increased cardiac output while total peripheral resistance was normal. 5. Although limited, the findings suggest that the initial step in the development of aldosterone-induced hypertension is a rise in cardiac output. This may be an important factor for the final elevation of total peripheral resistance.

1. On constant high (200 mmol)- and low (10 mmol)-sodium diets, thirty-one patients with idiopathic oedema have been compared with six non-oedematous control subjects while upright from 08.00 to 20.00 hours for 3 days and while recumbent all day for 2 days. 2. The cumulative weight rise in the upright posture and fall in recumbency were ‘normal’ in five patients (‘non-orthostatic oedema’) and excessive in twenty-six (‘orthostatic oedema’). 3. Leg volume showed a cumulative rise during the upright period, which was excessive in the orthostatic oedema patients only. 4. When the orthostatic oedema patients were in the upright posture, fifteen retained sodium excessively (‘orthostatic sodium retainers’), while eleven retained ‘normal’ amounts of sodium (‘orthostatic water retainers’). 5. The ‘orthostatic sodium retainers’ experienced excessive acute orthostatic falls in inulin and para-aminohippurate (PAH) clearances. Half of them showed excessive aldosterone excretion and secretion rates and excessive potassium excretion in the upright posture on the 200 mmol of sodium diet. Plamsa volume fell excessively after 1 h in the upright posture in these patients. None of these changes was significant or consistent in the other patients with oedema. 6. Plasma renin activity and plasma protein and albumin concentrations were ‘normal’ in all patients in all circumstances. 7. Idiopathic oedema is a group of disorders each associated with: (I) orthostatic fall in filtered sodium often with orthostatic hyperaldosteronism and consequent orthostatic sodium retention; (II) orthostatic water retention possibly related to orthostatic hypervasopressinism and occasionally associated with occult heart failure; or (III) non-orthostatic factors.

1. The disappearance rate of intravenously injected Evans Blue, plasma volume, cardiac output, and blood pressure were measured in seven normotensive and eighteen hypertensive subjects. 2. Plasma volume was found to be negatively correlated with the mean arterial pressure, Evans Blue disappearance rate and packed cell volume. 3. Faster disappearance rate of Evans Blue in hypertensive subjects may be due to an abnormality of mixing of the label or of the capillaries.

1. The New Zealand strain of rats with genetic hypertension (GH rats), the Japanese strain with spontaneous hypertension and the salt-sensitive strain of Dahl are now well established as three genetically pure lines for use in hypertensive research. Other pure lines not consciously selected for high blood pressure have also recently been shown to exhibit hypertension. 2. In the GH rats the inheritance of the blood pressure appears to be polygenic; thus a simple causation of the hypertension appears unlikely. The inheritance is also complex in the other pure lines of hypertensive rats. 3. In the GH rats variation in intake of sodium from 0.05% to 1% of the solid diet does not affect the development of the hypertension. 4. The renin-angiotensin-aldosterone system does not appear to play a primary role in the initiation of the hypertension in the GH rats. Compared with normotensive rats of the parent colony, plasma and renal renin are decreased, total exchangeable and carcass sodium are decreased, as are also the plasma volume and total extracellular fluid volume. Plasma sodium is normal and plasma potassium increased. 5. There is no evidence of a primary abnormality of catecholamine storage or turnover. Prevention of the development of the sympathetic nervous system from birth does not entirely abolish the difference in blood pressure between GH rats and comparably treated normotensive rats. 6. The increased peripheral resistance in blood-perfused hind limbs and tails of GH rats is due both to increased neurogenic and myogenic components and to a structural element. Increased vascular reactivity to a variety of constrictor agents is readily demonstrated in saline-perfused preparations. 7. The different strains of hypertensive rats may in their diversity mirror the differences between the various forms of human essential hypertension.

1. Measurements of plasma volume, haematocrit, extracellular fluid volume, blood pressure, venous pressure and interstitial tissue pressure were made in rats 4 days after unilateral nephrectomy. Measurements were repeated either 4 days after subsequent removal of the remaining kidney, or 4 days after anastomosis of the remaining ureter with the inferior vena cava. Extracellular fluid volume was expanded by giving 0.5% saline by mouth: in one series blood volume was expanded by injections of blood. 2. Plasma volume (PV) rose more after bilateral nephrectomy (BN), extracellular fluid volume (ECFV) more after unilateral nephrectomy and ureterocaval anastomosis (UNUCA). The PV/ECFV ratio was significantly higher after BN. 3. Blood pressure and venous pressure rose after BN but not after UNUCA. Interstitial tissue pressure (TP) rose more after BN in spite of greater expansion of interstitial fluid volume (IFV = ECFV-PV) after UNUCA. The ratio ΔIFV/ΔTP was several times less after BN than after UNUCA. 4. Interstitial space compliance was estimated by measuring changes in IFV and TP 10 min after a saline infusion (compliance = ΔIFV/ΔTP). After UNUCA there was little change from values obtained after unilateral nephrectomy alone; following BN compliance fell severalfold. 5. It is suggested that changes in compliance of the interstitial space may be brought about by a substance secreted by the kidney and represent a hitherto undetected mechanism by which plasma volume is maintained constant under different conditions of hydration. Changes in interstitial space compliance may also play a part in the aetiology of renoprival hypertension by raising tissue pressure, and thus venous pressure and cardiac output.

1. Rats of the New Zealand strain with genetic hypertension (GH rats) were found to have lower plasma volume in relation to body weight than rats of the normotensive parent strain (N rats). GH rats had higher venous packed-cell volume percentage than N rats, but total erythrocyte volume was similar in the two strains of rats. Extracellular fluid volume and exchangeable sodium concentrations were lower in the GH rats. Plasma sodium concentration was not altered; plasma potassium concentration was slightly higher in the GH rats. 2. These results indicate that hypersecretion of a sodium-retaining hormone is unlikely to be a primary factor causing hypertension in the GH rats. Cardiac output has not been measured: if an increased cardiac output is a factor in the maintenance of the hypertension, it is evidently not secondary to an increased blood volume. 3. The lower exchangeable sodium concentrations and body fluid volumes found in the GH rats may be due to lower aldosterone activity secondary to a decrease in the activity of the renin-angiotensin system, or to the effects of the elevated blood pressure on the renal handling of sodium, or to both factors.

1. Glomerular filtration rate was determined from 51 Cr—EDTA clearance in twenty hypertensive subjects treated with propranolol. 2. A significant mean decrease of 13% in the glomerular filtration rate was found during treatment, and an increase of the same order of magnitude after withdrawal of propranolol. 3. It is suggested that these changes are related to a reduction in the renal blood flow. 4. No significant changes were found in plasma volume.

1. Plasma albumin concentration was decreased in thirty-five of eighty-six mobilized para- or tetra-plegic patients studied months or years after injury to the spinal cord causing a medullary cross-sectional syndrome. The colloid osmotic pressure was low in thirty-one of eighty-one patients in whom it was measured. Plasma volume was normal in thirty and slightly elevated in three of thirty-three patients in whom it was determined. None had oedema at the time of the investigation. 2. Albumin metabolism was studied in ten patients by means of 131 I-labelled albumin. Six of these had a decreased plasma albumin concentration. This was probably caused by an increased fractional catabolic rate, although a statistically significant causal relationship could not be demonstrated. 3. in spite of the low plasma albumin concentration normal compensatory mechanisms such as an increase in rate of albumin synthesis and shift of albumin from the extravascular to the intravascular compartment were not found. On the contrary, for unexplained reasons, the average rate of synthesis and the ratio intravascular/total albumin mass were both decreased.

1. In ten patients with essential hypertension treated with propranolol (320 mg daily for 4 months) plasma volume and extracellular fluid volume were determined. 2. A significant increase in extracellular fluid volume (ECFV) was found, but there was no significant change in plasma volume. 3. The genesis of the increase found in ECFV is briefly discussed.