P39: Chronic sodium nitrite (NaNO2) therapy attenuates the severity of pressure overload induced heart failure in mice

Abstract

Background Nitric oxide (NO) bioavailability is reduced in the setting of heart failure. Nitrite (NO2) is a critically important NO intermediate that is readily metabolized to NO during various pathological states. We have previously demonstrated that sodium nitrite (NaNO2) ameliorates acute myocardial ischemia/reperfusion (MI/R) injury when administered at reperfusion and pretreatment with NaNO2 preconditions the heart against MI/R injury. However, no evidence exists as to whether increasing NO bioavailability via increased NO2 therapy attenuates pressure overload induced heart failure following transverse aortic constriction. Methods and results Transverse aortic constriction (TAC) was performed in male C57/BL6J mice (n = 13 per group) at 10–12 weeks of age. NaNO2 (50 mg/L) or saline vehicle (VEH) was administered daily in the drinking water post-operative day 1 for 9 weeks. Two-dimensional echocardiography was performed at baseline and at 1, 3, 6, and 9 weeks post (TAC) to assess left ventricular dimensions and left ventricular ejection fraction (LVEF). We observed significantly increased circulating and cardiac NO2 and nitrosothiol levels in mice treated with oral NaNO2. NaNO2 (50 mg/L) significantly preserved LVEF and improved left ventricular LV dimensions (LVEDD/LVESD; 3.5/2.2 mm vs. 4.8/4.0 mm, p Conclusions These results demonstrate that oral NaNO2 therapy or cardiac restricted eNOS gene therapy significantly increases nitrite (NO2) bioavailability, NO bioavailability, and confers significant preservation of cardiac structure and function during heart failure following TAC induced pressure overload. Disclosure Nothing to disclose.