The Role of Blood Pressure and Aldosterone in the Production of Hemorrhagic Stroke in Captopril-Treated Hypertensive Rats

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Abstract
Background and Purpose We tested the hypothesis that the lowering of plasma aldosterone levels contributed to the antistroke effects of captopril treatment in Wistar Kyoto stroke-prone spontaneously hypertensive rats (SHRSP). Methods The suppression of plasma aldosterone by captopril treatment (50 mg · kg –1 · d –1 ) was prevented by the subcutaneous infusion of aldosterone into captopril-treated SHRSP. We studied the effect this had on blood pressure (BP) and stroke development. Results SHRSP fed a Japanese-style diet containing 4% NaCl developed hypertension and a 100% mortality associated with intracerebral hemorrhage by 14 weeks of age. Captopril treatment from 6 weeks of age did not lower the BP but increased survival past 35 weeks of age. Hydralazine treatment (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-treated SHRSP to levels between those present in untreated pre- and poststroke SHRSP, the ability of captopril to retard stroke development was negated. The effects of aldosterone were mimicked by deoxycorticosterone (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. Conclusions Elevations in plasma aldosterone enhance stroke development within captopril-treated SHRSP through mechanisms that do not involve stimulation of mineralocorticoid receptors or the enhancement of hypertension. The antistroke effects of captopril treatment may be partially mediated through the suppression of plasma aldosterone.

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