Drug induced variations of the renin-angiotensin-aldosterone system in rats. II. Antihypertensives.

Summary Groups of male rats were treated with antihypertensive drugs (alpha-methyl-dopa, clonidine, propranolol, reserpine, diazoxide) which were administered under conditions causing the onset of high plasma renin activity (PRA) and high plasma and urine aldosterone levels, i.e. together with distilled water load (5% of body weight). Alpha-methyl-dopa and propranolol, which fail to significantly alter PRA and plasma aldosterone levels when administered without distilled water load, cause a marked decrease of plasma and urine aldosterone levels and of PRA when administered together with distilled water load, while diazoxide, and reserpine cause a marked increase of these values. Clonidine causes significant decreases of PRA and plasma aldosterone levels in both experimental situations. Increases of PRA and of plasma aldosterone levels occur also in rats treated with diazoxide associated with propranolol and in those treated with an association of reserpine and propranolol. The highest values of plasma aldosterone levels were found in rats treated with reserpine for two days and receiving a further dose of reserpine associated with propranolol on the third day, which fact was ascribed to the reduction of peripheral vascular resistance and of plasma flow in the kidney (as shown by decreased diuresis) brought about by propranolol and followed by a marked compensatory activation of the renin-angiotensin-aldosterone system. Moreover there is no apparent correlation between the antihypertensive effect and the variations of the renin-angiotensin-aldosterone system.