EFFECTS OF CAPTOPRIL RELATED TO INCREASED LEVELS OF PROSTACYCLIN AND ANGIOTENSIN-(1-7) IN ESSENTIAL-HYPERTENSION

Objective To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7) ] and prostaglandins to the acute and long-term antihypertensive actio ns of captopril in mild-to-moderate essential hypertensive patients De sign and methods Blood pressure, cardiac rate and the plasma concentra tions of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), pr ostaglandin E(2) and 6-keto prostaglandin F-1 alpha (the breakdown pro duct of prostacyclin) were determined in the peripheral venous blood o f 24 essential hypertensive subjects before and 3h after administratio n of 50 mg captopril. Eleven of 24 patients completed a 6-month treatm ent period with captopril monotherapy (50 mg twice a day). The hemodyn amic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pres sure control with captopril monotherapy for 6 months. Results The fall in blood pressure produced 3h after drug intake was comparable for th e first and the last 50 mg captopril dose, Although the first response to captopril increased plasma levels of Ang I only, the response to t he last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E(2) and 6-keto prostaglandin F-1 alpha were not modified by a first exposure to captopril, the con centrations of B-keto prostaglandin F-1 alpha but not prostaglandin E( 2) rose significantly in subjects treated with the inhibitor for 6 mon ths, A negative correlation was also demonstrated between diastolic bl ood pressure and plasma Ang-(1-7) levels in the 11 essential hypertens ive subjects in whom blood pressure was controlled with captopril mono therapy. Conclusions Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not dire ctly accounted for by a suppression of plasma Ang II levels, Continuou s therapy with captopril unmasked a contribution of Ang-(1-7) and pros tacyclin to the antihypertensive actions of this drug.