Abstract

The relationship between blood pressure lowering activity and inhibition of plasma and tissue angiotensin-converting enzyme (ACE) has been studied in the sodium deficient normotensive rat at 24, 48 and 96 h after the administration for 21 days of enalapril (MK-421, 10 mg/kg per day p.o.). Blood pressure was reduced and plasma ACE activity inhibited at 24 and 48, but not 96 h, after cessation of dosing. Tissue ACE activity (aorta, lung, mesenteric bed) was inhibited up to 96 h post dose when blood pressure had returned to control values. ACE production (activity following removal of inhibitor) was increased in plasma at 24, 48 and 96 h post dose but in tissues (adrenal glands, renal arteries and mesenteric bed) only at 48 h post dose. There was no tendency for ACE production to increase in the lung, the largest source of the enzyme in the rat. Thus it appears that inhibition of ACE activity in both plasma and tissue contributes to the blood pressure lowering activity of enalapril in the sodium deficient normotensive rat.

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