INHIBITION OF EITHER ANGIOTENSIN-CONVERTING ENZYME OR NEUTRAL ENDOPEPTIDASE INDUCES BOTH ENZYMES

Synthesis of angiotensin-converting enzyme is induced during its chron ic inhibition. Like angiotensin-converting enzyme, neutral endopeptida se (EC 3.4.24.11) is a plasma membrane peptidase. We studied changes o f the two enzymes in lung, kidney and serum in a coronary ligation mod el of experimental congestive heart failure, and during chronic inhibi tion of the enzymes. Coronary-ligated rats (n = 19) and sham-operated controls (n = 18) were given SCH 34826 yl]-2-phenylethyl]-L-phenylalan ine]-beta-alanine}, a specific neutral endopeptidase inhibitor (n = 13 ), captopril(n = 12), or vehicle (n = 12) for 4 days, and exsanguinate d. Pulmonary angiotensin-converting enzyme was induced both by captopr il (52% compared to vehicle) and by SCH 34826 (21%). Serum angiotensin -converting enzyme was induced by captopril (44%). Neutral endopeptida se was induced in lung by captopril (73%), and in kidney by SCH 34826 (32%). Compared to controls, the relative heart weight of rats with he art failure was increased by 29%, and the plasma level of atrial natri uretic peptide elevated by 74%, but enzyme activities were not differe nt. We conclude that, in the rat, separate inhibition of either angiot ensin-converting enzyme or neutral endopeptidase induces both enzymes, and that the induction varies in different tissues. Alterations in th e substrates of the two enzymes, e.g. in bradykinin, might cause these changes.