PINDOLOL DECREASES PLASMA ANGIOTENSIN CONVERTING ENZYME ACTIVITY IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

The renin-angiotensin systen is control led by a number of factors, among which beta-adrenoceptors are wel I understood. In turn, the antihypertensive action of bet a- ad renoc eptor blockers may be partial'ly due to antagonism of the renin-angiotensin systern (l ). Alterations of the renin-angiotensin system occur in spontaneously hypertensive rats (SHR). These anirnals show low angjotensjn converting enzj/me (ACE) activity in plasma (2). It has been postulated that plasma ACE is orjginated in lung, although endothelial cells in peripheral vessels could also make a contribution (3), Studies have shown that angiotensin II localiy produced 'in arterial tissues by ACE might be important jn maintaining vascul ar tone (4). We stud'ied the effects of pindolol , a non-selective beta-adrenoceptor blocker and 'lidely used anti hypertens ive drug, on plasma, lung and mesenteric artery ACt of young (4 to s-week-old, pre or early hypertensive) and adult (24 to 25-week-old) SHR. METHODS. Pindolol was given oral ly for 7 days once a day at a dose of l0 mg/kg body we'ight to male,4- and 24-week-old SHR and ldistar Kyoto (I,JKY) rats, Animals were decapitated 24 hr after the last treatment. ACE activity was measured by a radiochemical method (5). Lung and mesenteric arteries were homogenized jn 0.1 14 potassium phosphate buffer pH 8.0, by glass to g'lass tissue grinders. The homogenate was centrifuged at 130,000 x g for 30 minutes, yie'ldinq a pellet and a supernatant. The supernatant was considered to óe a loosely-bound (soluble) ACE containing fraction (F1 ). The pellet was resuspended in the buffer, containing 0.5% friton X-100, ultrasonicated, and frozen-thawed 3 times in order to solubilize the particulate enzyme (6). The homogenate was centrifuged at 10,000 x g for 30 minutes; the supernatant was referred as the F2 fraction (particulate).