The effct of propranolol on plasma renin activity and blood pressure in mild essential hypertension.

Fourteen male patients with mild to moderate essential hypertension have been studied with regard to plasma renin activity (PRA) after acute and prolonged /?adrenergic blockade with propranolol. Initial PRA was determined after four weeks of placebo treatment. Before propranolol was given PRA rose in response to 10 min of 45" head-up tilt from 151.7 ng/100 ml/h to 248.7 ng/100 ml/h ( p < 0.01). After acute administration of propranolol 0.22 mg/kg b.wt. i.v. and following repeated tilt for 10 min PRA only rose to 204.7 ng/100 ml/h (n.s.). Following four weeks of oral propranolol treatment at 160-320 mg daily PRA after tilt was 39.0 ng/100 ml/h. Thus a significant reduction (of PRA had taken place (p<0.005) to a level constitutial: only 15 % of the initial PRA after tilt. The reduction of blood pressure (BP) after four weeks of propranolol treatment was also significant. Diastolic BP was reduced by 19 mmHg(p< 0.001). The changes in BP and tilted PRA were not significantly correlated ( r = 0.449, p < 0.10). These results indicate that propranolol causes a marked reduction of PRA in addition to its hypotensive effect. However, this does not necessarily imply that there is a direct causal relationship between the effect of propranolol on PRA and its effect on BP. Usually, renin is not elevated in patients with nonmalignant essential hypertension (7, 12, 29) and aldosterone secretion is normal (7, 19). On the other hand, elevated renin levels and increased aldosterone secretion practically always occur in malignant hypertension (16, 17, 20). Already in 1960 Laragh et a]. suggested that the vascular damage seen in malignant hypertension was related to elevated levels of angiotensin (16, 17). Later animal studies have shown that excess renin/angiotensin may cause vascular lesions of the same appearance as those seen in malignant hypertension (5 , 8, 9, 22). Recently Laragh's group presented observations on 219 hypertensive patients followed for 10 years, ' Present address: Department of Internal Medicine I, Sahlgren's Hospital, University of Goteborg, Goteborg, Sweden. which indicated that low plasma renin was associated with a reduced risk of cardiovascular complications such as stroke and myocardial infarction (2). Others do not support this view (6). Based on observations by Laragh and coworkers (2), it would be logical to use antihypertensive therapy that not only reduces blood pressure (BP) but also lowers renin actively. Several of the antihypertensive drugs have been studied with regard to their effect on plasma renin activity (PRA). Thus diuretics ( 1 , 28), hydralazine (21), diazoxide (15) and sodium nitroprusside (14) have been shown to cause elevations of PRA, while drugs with adrenergic inhibitory effects may cause mild to moderate reductions of PRA. This has been demonstrated e.g. for methyldopa (23), clonidine (13, 24), phentolamine (30), propranolol (30) and alprenolol (4). As propranolol, at least in acute experiments, seems to be quite eflective in reducing PRA (3) and as the experience with propranolol in hypertension has been encouraging (11, 26, 31) the present study was designed to study the effect on PRA of acute and chronic /?-adrenergic blockade with propranolol in patients with essential hypertension.