Cardiac Function in Endothelial Nitric Oxide Synthase Knockout Mice with Heart Failure

Abstract

P57 Nitric oxide(NO)released by endothelial NO synthase(eNOS)is impaired during the development of heart failure (HF). We tested the hypotheses that 1)lack of eNOS (-/-) may affect cardiac function and remodeling after MI induced by coronary ligation; and 2) the cardioprotective efffect of ACEi will be lessened or absent in -/- mice. 1 month after MI, mice were treated with either vehicle or the ACEi enalapril (20 mg/kg) and this was continued for 3 months. C57BL6J (+/+) mice were used as controls. LV ejection fraction (LVEF), shortening fraction (SF), LV mass (LVm) and diastolic dimension (LVDd) were evaluated by echocardiography before and after MI. We found that LVEF (figure) and SF were decreased, and LVDd and LVm increased significantly after MI and slowly progressed with time. No difference was detected between the two strains. ACEi improved LVEF in +/+, but not in -/-; and they also decreased LVm and LVDd, and these effects were diminished in -/- mice. Our data suggest that eNOS may not play an important role in the development of HF; however, it does participate in the cardioprotective effects of ACEi.