1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function. 2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow. 3. Compared with patients with normal renal function, patients with chronic renal failure exhibited ( i ) unchanged transfer rate constants and distribution volumes, ( ii ) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance. 4. Analysis of data obtained after oral administration of the drug by the Loo—Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited ( i ) a significantly decreased fraction of dose effectively absorbed, ( ii ) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance. 5. The study provided evidence that in patients with renal insufficiency, ( i ) no increase in the metabolism of the drug accompanied the decrease in renal function, and ( ii ) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.

1. Cardiac haemodynamics were determined in 196 male untreated subjects, comprising 98 normotensive individuals and 98 hypertensive patients of the same age. 2. In order to study the haemodynamic change in hypertension, a new methodology was proposed. The whole population was classified by increasing diastolic pressures and divided into overlapping subgroups. From subgroup to subgroup, mean values of different haemodynamic variables were plotted against mean values of diastolic pressures. Three phases could be observed in the changes of these variables. In the first phase (for mean diastolic pressures under about 80 mmHg), the rise in pressure was associated with a decrease in blood volume and with an increase both in cardiac output and heart rate. In the second phase (for mean diastolic pressures between 80 mmHg and 95 mmHg approximately), heart rate, cardiac output and blood volume remained at the same values. In the third phase (for mean diastolic pressure above approximately 95 mmHg), heart rate remained elevated while the rise in pressure was associated with a decrease both in cardiac output and blood volume. 2. In the same subgroups, the correlations between cardiac output and heart rate and between cardiac output and blood volume were studied. The correlation between cardiac output and heart rate was significant only in normotensive ranges while the correlation between cardiac output and blood volume was significant only in hypertensive ranges. 3. Classical statistical tests, performed in distinct subgroups, confirmed the above observations on the changes of mean values and correlations. 5. The study provided evidence that cardiac output was predominantly controlled by neural mechanisms within the normotensive range and by volume mechanisms within the hypertensive range.

1. Blood pressure, blood volume and renal blood flow were determined in 101 men; forty-three were normal subjects and fifty-eight were untreated permanent essential hypertensive patients with normal renal function and equilibrated sodium balance. 2. A significant negative pressure—volume relationship was observed overall. The relationship could be expressed as a hyperbola whose slope expressed the reduction in blood volume per unit rise in pressure: the higher the blood pressure, the lower the slope. Thus essential hypertensive subjects have a smaller decrement in blood volume per unit rise in pressure than normal subjects. 3. The relation between change in blood volume and change in pressure was confirmed in each individual by defining for each a ratio Δ V /ΔP, statistically identical with the hyperbolic slope d V /dP. The Δ V /ΔP ratio was found to be well correlated with the renal blood flow and the creatinine clearance. No correlation existed between the total blood volume and these two renal parameters. 4. It is concluded that the present study demonstrates a blood volume regulation disturbance in essential hypertension and provides evidence from human studies that a renal defect accompanies high blood pressure.

1. The changes in plasma volume, haemodynamic variables, plasma renin activity and plasma aldosterone were studied in forty-one hypertensive patients after administration of adrenergic-blocking agents. Four drugs were used: alpha-methyldopa (fourteen patients), guanethidine (ten patients), clonidine (nine patients) and reserpine (eight patients). Drugs were administered orally during 7 days' hospitalization on a normal sodium diet (110 mmol/day). 2. The four drugs had similar effects: a significant decrease in blood pressure, a significant increase in plasma volume and no change in stroke volume. 3. With alpha-methyldopa and guanethidine, heart rate, plasma renin activity and plasma aldosterone were unchanged. 4. With reserpine and clonidine, heart rate and plasma renin activity were significantly decreased, whereas plasma aldosterone did not change significantly. 5. This study suggests that the decrease in plasma renin activity was related to the lowering of the heart rate rather than to sodium retention and that adrenergic-blocking agents can impair the normal relationship between stroke index and plasma volume, between plasma volume and plasma renin activity, and between plasma renin activity and plasma aldosterone.

1. A haemodynamic study which included estimation of cardiopulmonary blood volume (CPBV), total blood volume (TBV) and vascular reactivity to noradrenaline was performed in seventeen borderline and sixteen permanent hypertensive patients. 2. Borderline hypertensive patients had higher values of cardiac index, stroke index and heart rate when compared with the permanent hypertensive patients, and lower values of blood pressure and total peripheral resistance. 3. The CPBV/TBV ratio was significantly higher in borderline hypertensive patients. In that group, this ratio was directly correlated with cardiac index, stroke index and the pressor dose of noradrenaline ( P < 0.01). 4. In permanent hypertensive patients, none of these correlations was observed. Only the total blood volume was correlated directly with cardiac index and inversely with total peripheral resistance. 5. The study suggests that a redistribution of intravascular volume from peripheral veins to the cardiopulmonary capacitance bed occurs in borderline hypertension when compared with permanent hypertension and that hypertension is related to a neural mechanism in the borderline state and to a volume mechanism in the permanent state.