THE ROLE OF BLOOD-PRESSURE AND ALDOSTERONE IN THE PRODUCTION OF HEMORRHAGIC STROKE IN CAPTOPRIL-TREATED HYPERTENSIVE RATS

Background and Purpose We tested the hypothesis that the lowering of p lasma aldosterone levels contributed to the anti-stroke effects of cap topril treatment in Wistar Kyoto stroke-prone spontaneously hypertensi ve rats (SHRSP). Methods The suppression of plasma aldosterone by capt opril treatment (50 mg . kg(-1) . d(-1)) was prevented by the subcutan eous infusion of aldosterone into captopril-treated SHRSP. We studied the effect this had on blood pressure (BP) and stroke development. Res ults SHRSP fed a Japanese-style diet containing 4% NaCl developed hype rtension and a 100% mortality associated with intracerebral hemorrhage by 14 weeks of age. Captopril treatment from 6 weeks of age did not l ower the BP but increased survival past 35 weeks of age. Hydralazine t reatment (40 to 80 mg/L of drinking water) lowered BP in SHRSP but was less effective than captopril in retarding stroke. Plasma aldosterone levels were elevated with age in SHRSP after 10 weeks and were higher in poststroke versus prestroke SHRSP. Captopril treatment suppressed plasma aldosterone. When we elevated plasma aldosterone in captopril-t reated SHRSP to levels between those present in untreated pre-and post stroke SHRSP, the ability of captopril to retard stroke development wa s negated. The effects of aldosterone were mimicked by deoxycorticoste rone (40 mg/kg, SC2 times/wk) but not by dexamethasone (0.1 mg . kg(-1 ) . d(-1), SC). Spironolactone treatment (20 mg . kg(-1) . d(-1), SC) of SHRSP reduced BP but had little effect on stroke development. Concl usions Elevations in plasma aldosterone enhance stroke development wit hin captopril-treated SHRSP through mechanisms that do not involve sti mulation of mineralocorticoid receptors or the enhancement of hyperten sion. The anti-stroke effects of captopril treatment may be partially mediated through the suppression of plasma aldosterone.