Effect on prolonged inhibition of neutral endopeptidase on cardiac hypertrophy in rats with myocardial infarction

Cardiovascular Drugs and Therapy
C MarieJ Bralet

Abstract

Myocardial infarction was induced by rats by ligation of the left coronary artery. Treatment with TM1, a prodrug of SQ 28,603, an inhibitor of neutral endopeptidase (NEP, EC 3.4.24.11), was started 18-20 hours after ligation and was continued for 4 weeks (100 mg/kg, orally, twice daily). Morphological and biochemical parameters were assessed at the endo of therapy. The treatment resulted in a significant reduction of heart hypertrophy, which was restricted to the parts of myocardium hemodynamically upstream of the infarcted left ventricle. The weights of the right ventricle and atria were reduced by 15-20%, whereas the treatment had no effect on the left ventricle and septum weights. Treatment led to an almost complete inhibition of plasma NEP activity and to a slight decrease (-14%, p < 0.05) in plasma ACE activity. Plasma ANF level increased 3.8-fold after ligation, and treatment resulted in a slight ( + 29%) and nonsignificant additional increase in the ANF level. The amount of hydroxyproline in the right ventricle was enhanced by + 207% in control ligated rats and by +140% (NS) in treated rats. These data indicated that prolonged NEP inhibition exerts a favorable effect in heart failure by reducing the development of right ...Continue Reading

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Citations

Jun 23, 2000·Journal of the American Veterinary Medical Association·J R Turk
Aug 24, 2005·Journal of Cardiovascular Pharmacology·Virginie MellinPaul Mulder
Aug 3, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas WaltherCarsten Tschöpe

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