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1 The new converting enzyme inhibitor RHC 3659 was tested in 15 male volunteers. The study consisted of two parts: first, the ability of a single oral dose (5, 10, 20, 40 or 80 mg) to inhibit the pressor response to exogenous angiotensin I was tested with blood pressure and heart rate monitored continuously through an intraarterial catheter. A dose-related shift to the right of the pressor response curve to angiotensin I was observed with a peak occurring within 0.5 to 1 h. The pressor response to angiotensin II was unaffected. 2 In the second part, plasma renin and converting enzyme activity, angiotensin II and aldosterone were measured serially before and up to 8 h after administration of a single oral dose of RHC 3659. As expected. plasma angiotensin II and aldosterone fell within 30 min while plasma renin activity increased. Plasma converting enzyme activity was suppressed at 0.5 h in a dose-related manner with levels still below 30% of control 4 h following 80 mg of the inhibitor. 3 However, in vitro the enzyme-inhibitor complex seemed quited fragile since during storage of the plasma samples at -20 degrees C, converting enzyme activity increased significantly already within days (P less than 0.001, n = 28) and continued to rise for more than 2 months. This fragility may explain the seemingly lower potency of RHC 3659 when compared to captopril. No side effects were observed.

1 Nadolol excretion was studied in 24 patients with chronic renal failure. 2 The amount of nadolol excreted during the 120-h period after receiving the drug ranged from less than 1% in functionally anephric, patients up to 11.5% in patients with average creatinine clearance of 57.9 +/- 3.6 ml/min/1.73 m2. 3 Renal clearance of nadolol was found to correlate with creatinine clearance; nadolol elimination is retarded in patients with renal failure. 4 Nadolol serum half-life is prolonged in proportion to the remaining renal function. Therefore, dosage intervals in renal patients receiving nadolol should be adjusted to creatinine clearance. 5 Haemodialysis effectively reduced serum concentration of the drug; it may therefore be a useful therapy for drug intoxication.

1 Captopril (SQ14,225), an orally active inhibitor of angiotensin-converting enzyme, was administered to nine patients with essential hypertension. Plasma renin activity (PRA) was low in four, 'normal' in three and high in two patients. 2 In the hospital, captopril alone induced a significant drop in BP from 165 +/- 6/106 +/- 2 to 140 +/- 5/90 +/- 1 mmHb (P less than 0.001). PRA increased concomitantly (P less than 0.05), whereas plasma-converting enzyme activity (P less than 0.005) and plasma aldosterone (P less than 0.05) were reduced. 3 Six patients underwent chronic ambulatory therapy with captopril for a mean of 16 +/- 3 weeks. After discharge from the hospital, BP remained normalized but in five out of six patients this required additional diuretic therapy. 4 The results suggest that captopril alone or combined with diuretic therapy provides a new, efficient and well tolerated tool to treat patients with essential hypertension independently of their PRA level. It may turn out to be more effective in lowering BP than beta-adrenoceptor-blocking agents.

1 The effect of single oral doses of six beta-receptor antagonists on exercise-induced changes in double product (systolic blood pressure x heart rate) were studied in 25 human volunteers. 2 Three doses of propranolol, nadolol, oxprenolol, pindolol, timolol and atenolol were selected for study on the basis of in vivo beta-blocking potency. 3 Although all beta-blockers studied reduced the double product response to exercise, the pharmacodynamics of this effect differed markedly. 4 Pharmacodynamic half-lives, estimated for the drug tested, were 39 h for nadolol, atenolol 21 h, timolol 15 h, oxprenolol 13 h, propranolol 11 and pindolol 8 h. 5 These results suggest that the clinical choice of a beta-blocker with the least problems of compliance can be made on the basis of pharmacodynamics as well as pharmacological profile.