The physiological response to a chronically failing heart is the implementation of compensatory mechanisms intended to support blood pressure. These mechanisms, which are not fully understood, increase peripheral vascular tone, thus increasing the strain on the weakened myocardium. This study investigated the structure and function of small arteries from heart failure patients and controls without heart failure in an attempt to identify abnormalities associated with heart failure which may be related to these mechanisms. Small arteries were dissected from gluteal biopsies and studied using wire myography. Arterial morphological parameters were measured and concentration–response curves constructed for a number of vasoconstrictor and vasodilator agonists. Plasma concentrations of neuroendocrine hormones were also measured. There were no morphological differences between small arteries from control subjects and those from patients with chronic heart failure. In heart failure patients, vasoconstrictor responses to endothelin-1 were significantly reduced, although plasma endothelin-1 levels were increased. Arteries from heart failure patients also showed evidence of an impaired neuronal uptake mechanism, since blockade by cocaine had no effect on noradrenaline-induced vasoconstriction in these vessels. These results suggest that small-artery structure is not altered in chronic heart failure and so cannot account for the heightened vascular resistance in this syndrome. However, abnormal neuronal uptake and impaired vasoconstriction in response to endothelin-1 may be associated with the complex compensatory phenomenon involved in heart failure.

1. Resting and stimulated free calcium concentrations have been measured in platelets loaded with the fluorescent probe quin2 from 30 patients with essential hypertension and from 30 age-matched controls. 2. Cytosolic free calcium concentrations were 94.6 ± 2.7 (mean ± sem) in the hypertensive group and 91.7 ± 2.8 nmol/l in the normotensive group, the difference was not significant. 3. Arginine vasopressin caused a transient increase in platelet free calcium concentration in all subjects. In the presence of extracellular calcium the increase was significantly higher in the control subjects than in the hypertensive patients ( P = 0.005). In the absence of extracellular calcium, arginine vasopressin caused much smaller increases, and there was then no difference between the responses of the two groups. 4. Platelet free calcium concentrations were measured again in 13 patients after 8 weeks treatment with either verapamil ( n = 6) or atenolol ( n = 7). The reductions in systolic pressure after drug treatment were correlated with the changes in cytosolic free calcium concentrations ( r = 0.75, P < 0.01).

1. In the presence of calcium, both high- [dissociation equilibrium constant ( K d ) 5.8 × 10 −11 mol/l] and low-( K d 1.2 × 10 −8 mol/l) affinity binding of atrial natriuretic peptide was detected on plasma membranes prepared from sodium-depleted rats. 2. In contrast, under calcium-free conditions only high-affinity binding ( K d 6.9 × 10 −11 mol/l) was detected. 3. The requirement for calcium for low-affinity binding suggests a different mechanism of action than that for the high-affinity receptor.

1. High-dissociation equilibrium constant (20 pmol/l, receptor number 17 fmol/mg) and low-dissociation equilibrium constant (10 nmol/l, receptor number 5 nmol/mg) affinity binding sites for atrial natriuretic peptide have been identified in membrane preparations from rat mesenteric artery. 2. Tracer degradation was corrected for mathematically and binding data were analysed by a non-linear computer technique. 3. Non-atrial natriuretic peptide vasoactive hormones, angiotensin II, vasopressin and bradykinin, did not compete for the high-affinity site. Related peptides with either C- or N -terminal amino acids missing still competed, while peptides without an intact disulphide bridge did not compete. 4. Neither the addition nor the removal of calcium affected the affinity or density of binding sites. Also the non-hydrolysable guanosine triphosphate analogue 5-guanylylimidodiphosphate had no effect on either affinity or number of sites. 5. These results indicate the presence of a specific high-affinity vascular receptor for atrial natriuretic peptide which could interact with the hormone under physiological conditions. The mechanism of binding is uncertain but is unlikely to involve calcium- or guanosine triphosphate-associated regulatory sites.

1. Diurnal changes in plasma concentrations of atrial natriuretic peptide (ANP), renin, angiotensin II, aldosterone, Cortisol and antidiuretic hormone were investigated in seven normal volunteers studied under standardized conditions of dietary sodium, posture and physical activity. After completion of the diurnal study serial measurements of these variables were continued during, and on recovery from, a 2 day period of severe sodium depletion. 2. Clear diurnal variations in plasma concentrations of renin, angiotensin II, aldosterone, Cortisol and antidiuretic hormone were observed. 3. Plasma ANP concentrations also varied significantly over 24 h. Values peaked about mid-day and a distinct trough in peptide concentrations occurred in the early evening. However, variations in plasma ANP values were of relatively small amplitude and not clearly independent of modest parallel shifts in sodium balance. 4. Changes in plasma ANP concentrations both within the diurnal study period and during sodium deprivation were closely and positively correlated with concomitant changes in cumulative sodium balance. 5. No simple parallel or reciprocal relationships between plasma concentrations of ANP, on the one hand, and concurrent plasma concentrations of other hormones or in the rate of urinary sodium excretion, on the other, were observed during the 25 h of the diurnal study.

1. Chronic two-kidney, one-clip hypertensive rats were infused with captopril for 5 days and the daily variability of blood pressure compared with that for both hypertensive rats infused with glucose and normotensive animals. 2. Blood pressure was measured continuously using a computer data collecting system. 3. Normotensive animals showed a stable level of arterial pressure throughout each 24 h period with troughs occurring when they slept during the daytime. 4. Hypertensive animals given glucose had an enhanced diurnal rhythm of blood pressure compared with normotensive rats, with peaks occurring during periods of activity at night as well as troughs when they slept during the day. 5. Hypertensive rats given captopril retained this enhanced pressure variability, in spite of the fact that blood pressure was significantly lower and angiotensin II was suppressed. 6. These results suggest that angiotensin II is not involved in the increased blood pressure variability of renal hypertension and that some other irreversible mechanism is responsible.

1. The thirst and plasma vasopressin responses to single-blind controlled intravenous angiotensin II infusions (2-16 ng min −1 kg −1 ) were investigated in ten healthy young men. 2. Thirst and vasopressin secretion were stimulated in four out of ten subjects. These effects occurred at plasma angiotensin concentrations well above those measured under physiological conditions associated with thirst and vasopressin secretion such as water deprivation. 3. Further studies are needed to define why only certain individuals respond to intravenous angiotensin II infusions and to determine whether potentiation of angiotensin-induced thirst and vasopressin secretion by other stimuli (e.g. hypovolaemia and hypertonicity) might occur in man, in particular under pathological conditions when plasma angiotensin levels are above the physiological range.

1. Blood pressure, renin concentration and angiotensin II were measured in unanaesthetized two-kidney one-clip hypertensive rats at 1 and 2 days, at weekly intervals up to 10 weeks and at 15 and 20 weeks after clipping. 2. Compared with values in sham-operated rats, renin and angiotensin II were initially increased at 1–2 days but were then suppressed between 2 and 4 weeks to levels similar to that found in sham-operated rats. Between 5 and 20 weeks renin and angiotensin II increased again to high levels. 3. There was a significant correlation between angiotensin II and blood pressure in acute rats 1–2 days after clipping ( P < 0.05) and in chronic rats 8–20 weeks after clipping ( P < 0.001). There was no difference in the slope of the regression lines but the regression line for the chronic rats was shifted upwards in a parallel manner. 4. The acute hypotensive response (−20.3 ± sd 24.9 mmHg) in 26 chronic rats given converting enzyme inhibitor was related to the basal renin and angiotensin II levels and followed the slope of the angiotensin II/blood pressure regression line for all chronic rats. Only one out of 26 rats reduced its blood pressure to normal levels. 5. In 12 rats at 4 weeks after clipping, when blood pressure was elevated but angiotensin II was suppressed, there was only a small fall in blood pressure (−7.1 ± sd 7.2 mmHg). This also followed the angiotensin II/blood pressure regression line for chronic rats but at the lower end. Blood pressure again was not reduced to normal. 6. These results suggest that renin and angiotensin II are increased up to 20 weeks after clipping, that there is no change in the net vascular responsiveness to endogenous angiotensin II at any stage in this experimental model and that the acute effect of angiotensin II is determined solely by its position in the same dose—response curve. Also with the exception of 1–2 days immediately after clipping the acute effect of angiotensin II plays only a minor, though variable, role in the hypertension and that some other mechanism, as yet undetermined, is of greater importance and begins to have an effect as early as 2 weeks after clipping.

1. Arterial pressure, exchangeable sodium (Na E ), exchangeable potassium (K E ) and plasma concentrations of sodium, potassium, urea, angiotension II and aldosterone were measured in 34 patients with untreated Conn's syndrome before surgical removal of their adenoma. The study was repeated in 23 patients between 3 and 12 months after the operation. 2. Plasma aldosterone, Na E and plasma sodium concentration were higher and K E and plasma potassium concentration were lower than predicted normal. Surgery corrected these abnormalities, also reducing blood pressure from an average of 183/112 to 138/86 mmHg. 3. Systolic blood pressure was positively correlated with plasma and exchangeable sodium and negatively correlated with plasma potassium concentration. The relation of Na E and arterial pressure was closer in old than in young patients. None of these correlations was significant after operation. Before operation plasma urea was insignificantly related to arterial pressure but after operation a significant and positive correlation emerged. 4. A relation between arterial pressure and Na E is to be expected in a state of mineralocorticoid excess but the different correlation in old and young patients was not expected. A similar difference exists in patients with essential hypertension.

1. Angiotensin II was infused at stepwise increasing dose rates (2, 4 and 10 pmol min –1 kg –1 ) in 12 normal subjects. Infusions were performed in the presence of normocalcaemia, mild hypercalcemia induced by concomitant calcium gluconate infusion, and after 2 weeks of treatment with nifedipine. 2. Pre-infusion plasma levels of angiotensin II, renin or aldosterone were not altered by acute mild hypercalcaemia or administration of nifedipine. The angiotensin II-induced increases in plasma aldosterone were also similar under the three study conditions. 3. Variations in calcium metabolism occurring under clinical conditions appear to play a minor role in modulating the angiotensin II-dependent pathway of aldosterone regulation in normal man.

1. Potassium was infused intravenously in an incremental fashion and the plasma aldosterone responses were measured in conscious beagle dogs at five different intakes of dietary sodium. 2. Potassium/aldosterone dose—response curves were constructed for each dietary sodium regimen. 3. The rate of increase of plasma potassium during graded potassium infusion became progressively greater with increasing sodium depletion. 4. Regression lines of plasma aldosterone on plasma potassium were progressively elevated and steepened with increasing sodium depletion. 5. The alteration of these dose-response curves could in part have been the result of chronic elevation of plasma potassium and angiotensin II, and depression of plasma sodium, with sodium deprivation. 6. By contrast, acute changes in plasma angiotensin II or sodium concentrations across incremental infusions of potassium did not explain the progressive changes in the potassium/aldosterone dose—response curves. 7. The steepest part of the plasma aldosterone response curve was in the plasma potassium range 4–6 mmol/l. 8. Maximum achieved aldosterone levels were similar to or greater than those attained during angiotensin II infusion in previous studies in beagle dogs. 9. Potassium, like angiotensin II and adrenocorticotropic hormone, becomes a more effective stimulus to aldosterone with sodium depletion, thereby facilitating the preservation of sodium homoeostasis.

1. Arginine vasopressin was infused at 0.5, 2, 6, 18 or 54 ng min −1 kg −1 for 1 h into normal, sham-operated and DOCA—salt hypertensive rats. Complete vasopressin/blood pressure dose—response curves were constructed from circulating plasma vasopressin concentrations measured at the end of each infusion. 2. DOCA—salt hypertensive rats had a higher basal plasma vasopressin concentration (11.1 ± sd 3.7 fmol/ml) than either the normal (3.9 ± 2.3, P < 0.01) or the sham-operated rats (4.5 ± 2.4, P < 0.01). 3. The DOCA—salt hypertensive rats did not have any detectable enhancement of pressor sensitivity, compared with either of the two normotensive groups. 4. There was no significant increase in blood pressure in either the normal rats or sham-operated rats until vasopressin was infused at 2 ng min −1 kg −1 , when the plasma concentration was between 30 and 40 fmol/ml. 5. Subpressor infusion of vasopressin in the normal and sham-operated rats, which gave plasma concentrations of 22–23 fmol/ml, completely suppressed plasma angiotensin II to levels similar to the basal values found in the DOCA—salt hypertensive rats (10.5 ± 2.3, 14.5 ± 4.5 and 8.0 ± 1.6 fmol/ml respectively). 6. These findings suggest that the mechanism of vasopressin involvement in DOCA—salt hypertension is as yet unclear, that short-term changes in vasopressin concentration appear unimportant in the regulation of normal blood pressure, that small physiological changes of vasopressin in normal rats may be important in the regulation of renin secretion, and that the increase in vasopressin concentration seen in DOCA—salt hypertension may contribute to the suppression of renin and angiotensin II in this state.

1. Six male beagle dogs with carotid loops were infused with sodium chloride solution (150 mmol/l: saline) during control observations followed by dopamine infusion at various rates. Arterial blood samples were drawn during the control period and at the end of each period of dopamine infusion for the measurement of plasma dopamine, noradrenaline, adrenaline, renin, angiotensin II, aldosterone, vasopressin, electrolytes and packed cell volume. Blood pressure and pulse were recorded throughout. 2. The rate of infusion and plasma dopamine levels were closely correlated ( r = 0.99, P < 0.001). Plasma dopamine levels two to 20 times basal values produced no significant change in any of the other variables measured; levels 200 times basal values caused a significant increase ( P < 0.05) in plasma renin concentration; levels 2000 times basal values were associated with significant increases ( P < 0.05) in plasma renin and angiotensin II, packed cell volume and blood pressure, without significant changes in other measurements. 3. Circulating dopamine is unlikely to be important in the control of sodium and water metabolism.

1. We studied the effect of oral prazosin on blood pressure, plasma active renin and angiotensin II in 16 recumbent hypertensive patients between 09.00 and 12.00 hours. 2. In untreated patients there were no significant changes in blood pressure, plasma active renin or angiotensin II during the 3 h period. 3. After an initial dose of prazosin (2 mg) there was a significant fall in recumbent blood pressure with progressive increases in plasma active renin and angiotensin II concentrations. 4. After 3–4 weeks' treatment with oral prazosin only, recumbent blood pressure at 09.00 hours, 15 h after the last dose of prazosin, was significantly lower than before treatment, but plasma active renin and angiotensin II were not significantly different from untreated values. 5. After the usual morning dose of prazosin, blood pressure did not change, but there were significant rises in plasma active renin and angiotensin II, less marked than after the first dose of prazosin. 6. Prazosin therefore stimulates the renin—angiotensin system acutely, both after the initial dose and during long-term therapy; however, no effect on renin and angiotensin II is apparent 15 h after the last dose of prazosin.

1. Plasma levels of vasopressin were found to be significantly higher in 29 patients with malignant hypertension than in 106 normotensive control subjects (13 ± 2 ng/l vs 5.8 ± 0.2 ng/l, P < 0.001). 2. No correlation was apparent between blood pressure and circulating vasopressin. 3. An acute, incremental infusion of vasopressin (0.125, 0.25 and 0.5 ng min −1 kg −1 ) in nine patients with mild-moderate essential hypertension produced only minor changes in blood pressure despite achieving plasma levels spanning those seen in malignant hypertension. 4. Despite a small increase in pressor sensitivity to vasopressin in hypertensive subjects it is thus unlikely that an acute vasoconstrictor effect of this peptide is important in the pathogenesis of malignant hypertension.

1. Captopril infused into sodium-loaded dogs produced a fall in both blood pressure [117 ± 9.7 to 96.6 ± 11.4 (sd) mmHg] and plasma angiotensin II [11.0 ± 3.0 to 1.6 ± 1.3 (sd) pmol/l]. Plasma aldosterone fell while both blood angiotensin I and renin concentration rose. 2. Angiotensin II was infused at 2, 6, 18 and 54 ng min −1 kg −1 into sodium-depleted dogs. Plasma angiotensin II and arterial pressure both rose and were related in a dose-response curve. 3. On a separate occasion the same dogs were given an intravenous infusion of captopril (6 mg h −1 kg −1 ) and the angiotensin II infusion was repeated. Again plasma angiotensin II and arterial pressure rose but the dose-response curve was displaced downwards; a higher concentration of angiotensin II being required to produce the same blood pressure as in the dogs not given captopril. 4. These findings suggest that the acute hypotensive effect of captopril is not wholly explained by a decrease in plasma angiotensin II concentration and the consequent reduction of its acute vasoconstrictor effect.

1. Changes in arterial blood pressure, blood angiotensin I, plasma angiotensin II and plasma angiotensin III were measured in conscious sodium—depleted dogs after infusion of captopril, an orally active inhibitor of converting enzyme. 2. Angiotensins II and III were measured after chromatography to remove angiotensin I, which increased in concentration after inhibition of converting enzyme and which interfered in the direct assay for angiotensin II. 3. Infusion of captopril at 20, 200, 2000 and 6000 μg h −1 kg −1 , each for 3 h, produced a rapid fall in blood pressure and in concentration of angiotensin II. Angiotensin II was undetectable at 6000 μg h −1 kg −1 (mean pre-infusion value for all samples was 39 ± sd 15 pmol/I, n = 14) 4. The percentage fall in blood pressure correlated with the percentage fall in plasma angiotensin II ( r = 0.65, P <0.001) 5. These results suggest that the initial fall in blood pressure may be mediated in part by the suppression of angiotensin II. 6. Blood angiotensin I concentration rose with each rate of infusion of drug to a maximum 16-fold increase at 6000 μg h −1 kg −1 (26−416 pmol/l). The rise in angiotensin I was inversely related to the fall in angiotensin II ( r = −0.68, P <0.001)

1. Captopril given for 5 days caused a fall in blood pressure in normotensive subjects. The percentage fall in mean supine pressure was greatest on a low sodium diet (10 mmol/day), 19.6%, least on a high sodium diet (350 mmol/day), 11%, and in between on a normal sodium diet (120 mmol/day), 16.5%. 2. Captopril caused a marked fall in plasma aldosterone in normal subjects on all three sodium intakes. 3. Captopril caused an increase in sodium excretion on the normal (120 mmol/day) and low (10 mmol/day) sodium diet but not the high sodium diet. 4. These results suggest that the renin-angiotensin-aldosterone system is a normal mechanism for maintaining blood pressure and aldosterone secretion in normotensive man. The system may also be involved in the maintenance of sodium balance. 5. These results may lead to a better understanding of the role of the renin-angiotensin-aldosterone system in the maintenance or causation of high blood pressure in essential hypertension.

1. Concentrations of angiotensin II (ANG II) were measured by radioimmunoassay in cerebrospinal fluid and plasma from neurosurgical patients and patients having spinal anaesthesia. Cerebrospinal fluid concentrations of renin, renin substrate and ANG I were also measured. 2. Cerebrospinal fluid concentrations of ANG II measured with antiserum 30/VI were low in neurosurgical patients (mean 6 pmol/l, range < 2-12 pmol/l, n = 7) and lower in spinal anaesthesia patients (mean 1 pmol/l, range < 2–4 pmol/l, n = 14) and unrelated to concurrent plasma concentrations of ANG II. 3. A second more sensitive immunoassay with ANG II antiserum 9/P gave higher cerebrospinal fluid concentrations of ANG II in spinal anaesthesia patients (mean 15 ± 1 pmol/l, n = 7, P < 0.01). 4. Paper chromatography showed that the ANG II immunoreactive material measured with antiserum 9/P was not ANG I, ANG II, ANG II-(2-8), ANG II-(3-8) or ANG II-(4-8). 5. The concentration of ANG I in cerebrospinal fluid was low (4 ± 0.04 pmol/l, n = 7). No renin was detected ( n = 32) and the concentration of renin substrate was 45 ± 2.6 nmol/l ( n = 24). 6. Much of the immunoreactive ANG II in human cerebrospinal fluid is an immunoassay artifact

1. Arterial pressure and exchangeable sodium (Na E ) were measured in patients with Conn's syndrome, essential hypertension, renal artery stenosis and chronic renal failure. Comparison was made with a control group. Urine sodium excretion was measured separately from the two kidneys in patients with renal artery stenosis. 2. Compared with control, mean Na E was significantly increased in Conn's syndrome, and was normal in essential hypertension, renal artery stenosis and chronic renal failure. 3. The correlation of arterial pressure with Na E was positive and significant in Conn's syndrome, essential hypertension and chronic renal failure. 4. In contrast the correlation was significantly negative in unilateral renal artery stenosis. Patients with lowest Na E had hyponatraemia, hypokalaemia and secondary hyperaldosteronism. 5. Urinary sodium excretion from the unaffected kidney in unilateral renal artery stenosis correlated positively with arterial pressure, possibly reflecting the phenomenon of pressure-natriuresis. Patients subsequently responding least well to surgery excreted least sodium from the untouched kidney for a given arterial pressure. 6. The findings suggest important roles for arterial pressure in the regulation of sodium balance (predominant in renal artery stenosis), and for sodium balance in the regulation of arterial pressure (predominant in Conn's syndrome). The observations in essential hypertension are compatible either with an exact balance between these mechanisms or with the existence of some other mechanism raising blood pressure.

1. The converting-enzyme inhibitor captopril has been given in doses up to 450 mg daily to hypertensive patients with renal artery stenosis and to patients resistant to other therapy. 2. Captopril alone was effective in controlling hypertension in renal artery stenosis, irrespective of whether pretreatment plasma angiotensin II was raised or normal, except in one man with overall renal impairment. 3. In one woman with the hyponatraemic hypertensive syndrome secondary to renal artery thrombosis, captopril restored depleted exchangeable sodium and potassium to normal. In the other cases of renal artery stenosis with normal renal function, exchangeable sodium and total body potassium were not significantly altered, and there were no marked changes in plasma sodium and potassium. 4. The combination of captopril with a diuretic controlled blood pressure long-term in every case of previously resistant hypertension. 5. Within 2 h, captopril induced highly significant falls in arterial pressure, in plasma angiotensin II and aldosterone, with converse increases in plasma active and total renin and blood angiotensin I. 6. The initial fall in plasma angiotensin II was closely related to the concomitant fall in diastolic pressure. 7. The pattern of change in circulating renin, angiotensins I and II and aldosterone was maintained during long-term therapy, whether or not a diuretic was added. There was no tendency for plasma angiotensin II to increase despite sustained elevation of active renin and angiotensin I.

1. A patient presented with mild hypertension, a raised plasma total renin concentration but a normal plasma angiotensin II concentration. The discrepancy was due to a high concentration of inactive renin in the plasma. 2. A renal carcinoma was detected and removed. The tumour contained a higher proportion of inactive renin than was found in uninvolved areas of the kidney. After unilateral nephrectomy, the plasma concentration of inactive renin fell to normal. 3. Six months later, plasma inactive renin concentration again increased and a metastasis was detected in a rib. Excision of the rib together with radiotherapy resulted in a fall in plasma inactive renin to normal. 4. The inactive renin in plasma and tumour extracts was activated to the same extent by acid treatment and by trypsin.

1. Infusion of angiotensin II into dogs at constant dose over 2 weeks caused a progressive rise in arterial pressure. 2. When the infusion was stopped the pressure dropped slowly from hypertensive levels over 48 h. 3. Dose—response studies at weekly intervals showed progressive elevation, without steepening, of the plasma angiotensin II—blood pressure curve. 4. Thus, during prolonged administration of angiotensin II, a given plasma concentration of the peptide can sustain a higher arterial pressure than it can during acute infusions.

1. Labetalol, a compound with both α- and β-adrenoreceptor-blocking actions, was given intravenously (1·5–2·0 mg/kg) in twenty recumbent hypertensive patients. 2. There was a rapid reduction in systolic and diastolic pressures in all, maintained up to 24 h in some subjects. 3. Severe hypotension was not seen in recumbent subjects, but postural hypotension was common. 4. Labetalol caused significant lowering of heart rate. 5. Labetalol induced significant and related lowering of plasma angiotensin II and aldosterone concentrations, most obviously when these were initially high. 6. In a cross-over comparison in five patients against 10 mg of propranolol intravenously, labetalol was more effective in lowering blood pressure, but less effective in lowering pulse rate or plasma angiotensin II.

1. Angiotensin II together with any immunoreactive fragments of angiotensin were measured in arterial and venous plasma before and during infusion of angiotensin II amide in five normotensive subjects, both in sodium-replete and sodium-depleted states. Because the antibody used in the radioimmunoassay cross-reacted with larger angiotensin breakdown products and because these fragments are present in higher concentrations in venous than arterial plasma, samples of both were assayed. Measurements on venous plasma are referred to as immunoreactive material (IM). 2. Arterial plasma angiotensin II concentration (PAC) and venous IM were compared in two additional subjects during infusion of angiotensin II amide and of synthetic human angiotensin II. 3. Arterial PAC and venous IM increased in linear relation to the dose of angiotensin infused, similar results being obtained with angiotensin II amide and synthetic human angiotensin II. 4. Before infusion, venous IM and arterial PAC were comparable (A:V ratio = 0·99 ± 0·16, n = 29). During infusion venous IM was consistently lower than arterial PAC; with angiotensin II amide the A:V ratio was 1·72 ± 0·49 ( n = 35), and with synthetic human angiotensin it was 1·63 ± 0·2 ( n = 6). 5. Results of an in vitro study suggest that the formation of new angiotensin in the vein is not sufficient to explain the lower A:V ratio of PAC before infusion. 6. It is proposed that arterial PAC rather than venous IM should be measured when the relationship between blood levels and biological effects of the peptide are the object of the study, particularly during angiotensin infusion or when rapid changes in circulating angiotensin occur.