Evidence for a vasodepressor effect of the angiotensin-converting enzyme inhibitor, MK421 (enalapril), independent of blockade of angiotensin II formation.
The effects of acute and chronic angiotensin-converting enzyme (ACE) inhibition with MK421 (enalapril maleate) on angiotensin II formation were studied in sodium-restricted rats. Male Sprague-Dawley rats were placed on a low-sodium diet (less than 0.04 mEq Na+/24 h) with daily injections of furosemide (1 mg/kg i.p.) for 5 days, and were studied at either 5 days or 3 weeks. Half the rats were given MK421 (300 mg/L) in the drinking water. Parallel groups of rats were fed a standard diet (0.26 mEq Na+/24 h) without MK421. As expected, rats maintained on the low-sodium regimen for either 5 or 21 days had marked stimulation of plasma renin activity and increased angiotensin I, angiotensin II, and aldosterone formation. When MK421 was added to the drinking water, there was inhibition of angiotensin II formation at 5 days (low sodium, 99.4 +/- 25.8 pg/ml; low sodium + MK421, 26.3 +/- 10.5 pg/ml; p less than 0.02), but angiotensin II formation at 3 weeks was not different from the control group (low sodium, 499 +/- 147 pg/ml; low sodium + MK421, 306 +/- 110 pg/ml). Plasma aldosterone levels closely paralleled those of angiotensin II in all groups (r = 0.94, p less than 0.05) compatible with angiotensin II stimulation of aldosterone production, even in the face of ACE inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
D000803:Angiotensin I / Q000096:biosynthesis; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004039:Diet, Sodium-Restricted; D004151:Dipeptides / Q000494:pharmacology*; D004656:Enalapril; D006400:Hematocrit; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects; D012711:Serum Albumin, Radio-Iodinated; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D012711:Serum Albumin, Radio-Iodinated; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I