Effects of alatriopril, a mixed inhibitor of atriopeptidase and angiotensin I-converting enzyme, on cardiac hypertrophy and hormonal responses in rats with myocardial infarction. Comparison with captopril.
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| Abstract |
The aim of the study was to compare, in a rat model of congestive heart failure, the effect of captopril, a selective angiotensin-converting enzyme (ACE; EC 3.4.15.1) inhibitor, to that of alatriopril, a mixed inhibitor of ACE and atriopeptidase (EC 3.4.24.11), an enzyme implicated in the degradation of atrial natriuretic factor (ANF). Myocardial infarction was induced by ligation of the left coronary artery. Groups of rats received orally twice daily captopril (10 mg/kg), alatriopril (100 mg/kg) or vehicle. Treatments were started 18 to 20 h after ligation and continued for 4 weeks. Hypertrophic and hormonal changes reflecting congestive heart failure were assessed in rats with large infarcts by measuring the relative weight of cardiac tissues as well as by assaying ANF in heart and plasma and by measuring renin activity in plasma. Both treatments significantly reduced cardiac hypertrophy, but alatriopril showed a greater efficacy than captopril--the increase in relative heart weight reaching 38% with captopril and only 22% with alatriopril (P < .05). The hypertrophy of right ventricle was reduced by 47% with alatriopril and by 35% with captopril (N.S.), whereas the corresponding reductions for atria were 47% vs. 21% (P < .05). Both treatments prevented the ligation-induced increase of ANF level in the right ventricle. In contrast, plasma ANF level was significantly reduced after captopril but not after alatriopril treatment, a difference that probably reflects the protection of endogenous ANF in circulation resulting from atriopeptidase inhibition. Plasma renin was increased by 36-fold after captopril but only by 1.6-fold after alatriopril, a difference that presumably reflects the inhibition of renal renin secretion by endogenous ANF after alatriopril. These data suggest that enhancement of ANF levels in circulation via atriopeptidase inhibition magnifies the capacity of ACE inhibitors to prevent cardiac hypertrophy, and they show the potential therapeutic value of mixed ACE-atriopeptidase inhibitors in congestive heart failure.
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| Authors | J Bralet, C Marie, C Mossiat, J M Lecomte, C Gros, J C Schwartz |
| Journal | The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 270 Issue 1 Pg. 8-14 (Jul 1994) ISSN: 0022-3565 [Print] United States |
| PMID | 8035346 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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