1. The effect of prolonged administration of β-adrenoreceptor-blocking agents was studied in growing rabbits. Equivalent doses of propranolol and timolol were given parenterally for 8 weeks. 2. Animals given propranolol had a significantly lower heart rate than that in the controls. After subcutaneous injection, plasma propranolol levels were twice those obtained after intraperitoneal injection. 3. Growth rate of animals given propranolol intraperitoneally was significantly less than controls, whereas animals given propranolol subcutaneously or timolol intraperitoneally grew normally. Reduced growth rate was associated with reduced food intake and was not related to the β-adrenoreceptor-blocking activity of the drugs. 4. At the end of the experiment the heart and other organs were examined. β-Adrenoreceptor blockade produced no significant changes in ventricular size or water content, and no significant changes in ultrastructure were found.

1. Sensitivity of the sino-aortic baroreflex was investigated before and after acute (23 patients) and chronic (23 patients) β-adrenoreceptor antagonism in patients with essential hypertension. 2. Sensitivity was inversely related to age ( r = −0·60) and systolic blood pressure ( r = −0·46); a positive relationship was noted between sensitivity and initial pulse intervals ( r = 0·40). 3. Sensitivity increased significantly in patients less than 40 years of age after chronic treatment. No change occurred after acute treatment or in older patients treated chronically. 4. The fall in ambulatory intra-arterial blood pressure after chronic treatment was unrelated to alteration of baroreflex sensitivity.

1. In eight patients with essential hypertension (EHT) and six patients with renovascular hypertension (RVHT) peripheral venous enzymatically active and inactive renin values were followed after acute stimulation of renin release by the vasodilating agent diazoxide (300 mg intravenously). Active renin rose during the first hour after diazoxide and remained high during the following 15 h, but inactive renin fell during the first hour and rose thereafter. Peripheral venous active and inactive renin were not different from arterial values both before and after diazoxide. 2. Sixteen patients with EHT received propranolol, 80 mg, four times a day. Six of them had a first injection of diazoxide the day before propranolol was started and a second one after 10–14 days of propranolol treatment. Peripheral vein active renin was lowered by propranolol, but inactive renin was raised. Both the diazoxide-induced rapid rise of active renin and the fall of inactive renin observed in untreated patients were absent during treatment with propranolol. 3. In four patients with EHT and seven patients with RVHT renal vein sampling was performed before and 30 min after diazoxide. Increased release of active renin from kidneys that were not markedly contracted was associated with a fall of the renal vein to peripheral vein ratio of inactive renin to a value less than one. 4. It is concluded that under certain circumstances stimulated release of active renin is associated with removal of inactive renin from the circulation by the kidney. This may in fact be due to intrarenal transformation of circulating inactive renin into its active counterpart. The findings suggest that a β-adrenoreceptor might be involved in this activation process.

1. In chloralose-anaesthetized dogs, central venous and arterial angiotensin (AII) levels were monitored by blood-bathed bioassay during venous haemorrhage of 20 ml/kg, acute renal ischaemia induced by suprarenal aortic stenosis and frusemide-induced diuresis. 2. Blockade of intrarenal dopamine receptors with ergometrine reduced markedly the increments in arterial AII associated with haemorrhage or suprarenal aortic stenosis, but did not consistently affect the corresponding increments in venous AII. 3. Ergometrine or renal denervation did not affect the increases of blood AII associated with frusemide diuresis. 4. Blockade of β-adrenoreceptors with propranolol, by contrast, reduced blood AII increments associated with all three procedures. 5. It is suggested that renin release during moderate haemorrhage and acute suprarenal aortic stenosis is, in the dog, partly due to activation of intrarenal dopaminergic nerves. 6. The possibility is discussed that propranolol may depress renin release in the dog by an action other than that of blocking β-adrenoreceptors.

1. Serial measurements of plasma renin activity (PRA), plasma aldosterone concentration (PA) and blood pressure were performed overnight in patients with borderline (group 1) and sustained essential hypertension (group 2) before and after acute and chronic administration of either propranolol or pindolol. 2. Group 1 patients exhibited a typical rhythm of recumbent PRA with low values before midnight and large increases early in the morning. 3. In contrast, no rhythm and very low PRA values were observed in patients of group 2. Blood pressure was higher in group 2 than in group 1. There was a significant correlation between the hyporeninaemic and hypotensive effect of either acute ( r = 0·79) or chronic ( r = 0·4) β-receptor blockade. 4. In group 1, after β-receptor blockade the day—night profile of renin was similar to that observed in group 2 before treatment. Thus, in this latter subgroup, low-renin profiles might reflect reduced β-adrenoreceptor activity. 5. Plasma aldosterone was lower in group 2 but appeared to be inappropriately high relative to renin. 6. The data suggest that in hypertensive patients classified according to their blood pressure and recumbent PRA profiles a significant relationship exists between changes in PRA and arterial pressure. Thus patients with high PRA respond better to treatment than patients with low renin. We conclude that in the patients studied sympathetic nervous system activity mainly determined renin values as well as anti-hypertensive effectiveness of the β-blocking drugs.

1. Labetalol (AH 5158) is a new drug which has both α- and β-adrenoreceptor antagonist activity. Labetalol has been compared with propranolol and placebo for the treatment of mild to moderate hypertension (150/100 to 189/114 mmHg), in a double-blind cross-over trial with three 10 week treatment periods. 2. Both drugs reduced blood pressures in nine of the ten patients who have completed the trial. Relative to placebo labetalol caused decreases in supine pressures similar to those caused bypropranolol (average −10/ −10 and −10/ −9 mmHg respectively), with a greater effect on standing (labetalol −20/ −19; propranolol −8/−12 mmHg; P < 001) and after exercise (labetalol −27/−18 and propranolol −16/−14 mmHg). 3. Labetalol and propranalol caused a similar fall in supine pulse rate (−11/min and −13/min respectively), but there was less bradycardia on standing (labetalol −11/min; propranalol −18/ min; P < 0001) and after exercise (labetalol −17/min; propranolol −23/min; P < 0·001). 4. The average dose ratios of labetalol to propranolol was 2·4:1 (w/w). 5. These results suggest that the effect of labetalol on blood pressure involves both α- and β-adrenoreceptor antagonist properties. 6. Further evaluation of labetalol is warranted as it may have some advantages in respect of producing less bradycardia, improved peripheral blood flow and less effect on airways resistance than ‘pure’ β-receptor-blocking agents.

1. By the use of a mechanical graded sieving technique a high yield of isolated glomeruli has been obtained from rat kidney. 2. Microscopy and renin assay have shown the presence of renin-containing juxtaglomerular cells attached to these glomeruli. 3. The viability of isolated glomeruli has been confirmed by the ability of the cells to survive and divide in tissue culture and by their exclusion of vital dyes. 4. In superfusion after washout of extracellular renin, the glomeruli actively release constant amounts of renin over 3 h in direct proportion to the number superfused. 5. Decreasing sodium concentration from 140 to 110 mol/l with constant osmolarity of 305 mosmol/l stimulated renin release by a direct effect on juxtaglomerular cells. 6. Catecholamines stimulated renin release in vitro in proportion to the potency of their action on β-adrenoreceptors. 7. The system of superfusion of isolated glomeruli provides a technique for studying the influence of mediators leading to renin release acting directly on juxtaglomerular cells, independent of pressure change, tubular sodium, the sympathetic nervous system and circulating hormones.