Inhibition of angiotensin-converting enzyme with quinapril (CI-906): investigation of antihypertensive mechanisms in spontaneously hypertensive rats

P Saynavalammi, I Porsti, AK Nurmi, E Seppala, T Metsa-Ketela, L Tuomisto, V Manninen and H Vapaatalo

Treatment for 8 days with a new nonsulfhydryl angiotensin-converting enzyme inhibitor, quinapril (CI-906), produced a marked and progressive reduction in the blood pressure of spontaneously hypertensive rats. Quinapril was given p.o. in a dose of 20 or 40 mg/kg once daily. Both doses increased plasma renin activity and decreased the urinary excretion of aldosterone. These results, together with a marked decrease in serum angiotensin-converting enzyme activity, indicate that the drug produced a considerable fall in circulating angiotensin II. The urinary excretion of vasopressin was not altered by the smaller dose of quinapril but was reduced by the larger dose, which increased water intake and urine excretion. Quinapril did not affect plasma kininogen or the urinary excretion of kallikrein. The urinary excretion of neither the prostacyclin metabolite 6-keto-prostaglandin F1 alpha nor the thromboxane metabolite thromboxane B2 were altered by the drug. However, quinapril did produce a temporary decrease in the excretion of prostaglandin E2, the effect passing off with the continuation of the treatment. These data indicate that vasodilatory prostanoids do not contribute to the blood pressure lowering effect of quinapril in spontaneously hypertensive rats. The inhibition of the renin- angiotensin system is probably the principal mechanism of the drug's antihypertensive action, but these results do not rule out the possibility that an increase in vasodilatory kinins may also be involved.

Volume 237, Issue 1, pp. 246-251, 04/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

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