EFFECTS OF CHRONIC TREATMENT WITH CAPTOPRIL(SQ 14,225), AN ORALLY ACTIVE INHIBITOR OFANGIOTENSIN I-CONVERTING ENZYME, INSPONTANEOUSLY HYPERTENSIVE RATS

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Abstract
The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225 [D-3-mercapto-2-methylpropanoyl-L-proline]) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+ and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 wk, 3 or 6 mo. Captopril caused progressive cumulative reductions in blood pressure, causing normalization of pressure after 6 mo. of dosing. Hydralazine significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2- to 3-fold after hydralazine and 15-fold after captopril. Hydralazine and captopril did not have consistent effects on 24 h urine volume, urinary Na+,K+ or aldosterone excretion. Apparently chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.