Cardioprotection by long-term ETA receptor blockade and ACE inhibition in rats with congestive heart failure: mono- versus combination therapy

摘要: Objectives: We investigated the effects of long-term endothelin A (ETA) receptor blockade and ACE inhibition, either alone or in combination, on hemodynamics, neurohormonal activation cardiac remodeling rats with congestive heart failure (CHF) after extensive myocardial infarction (MI). Methods: Rats were treated placebo, ETA antagonist LU135252 (30 mg/kg/d), inhibitor trandolapril (0.3 a combination both for 11 weeks, starting 7 days MI. Results: Despite comparable left ventricular (LV) systolic pressure among all drug treatments, only combined inhibition significantly reduced LV end-diastolic ( P <0.01), improved d /d t max <0.01) normalized sympathetic <0.05) CHF. The therapy was more effective reducing type I III collagen mRNA levels, MMP-2 zymographic activity accumulation surviving myocardium. Moreover, increases β-myosin heavy chain skeletal α-actin mRNAs, markers hypertrophy failure, attenuated to greater degree by than monotherapy, whereas right ANF upregulation prevented inhibition. Conclusion: Long-term MI effectively monotherapy. show additive fibrosis fetal gene expression. antagonists could be therapeutical option CHF addition an inhibitor.