Abstract 16615: Sodium Nitrite Improves Left Ventricular Function During Heart Failure via Cytoprotective Signaling and Angiogenesis
Background: Nitric oxide (NO) bioavailability is reduced in the setting of heart failure. We have previously demonstrated that sodium nitrite ameliorates acute myocardial ischemia/reperfusion (MI/R) injury when administered at reperfusion. However, no evidence exists as to whether increasing NO bioavailability via sodium nitrite therapy attenuates heart failure severity.
Methods and Results: Serum from heart failure patients exhibited significantly decreased nitrosothiol and cGMP levels. Transverse aortic constriction (TAC) surgery was performed in mice. Sodium nitrite (50 mg/L) or saline vehicle (VEH) was administered daily in the drinking water post-operative from day 1 for 9 weeks. Echocardiography was performed at baseline and for 9 weeks post TAC to assess LV ejection fraction (LVEF%). We observed significant increases in cardiac NO, nitrosothiol, and cGMP levels in nitrite treated animals. Sodium nitrite preserved LVEF at 9 weeks (p < 0.001 vs. VEH). In addition, circulating and cardiac tissue brain natriuretic peptide (BNP) levels were attenuated in mice receiving nitrite (p < 0.05 vs. VEH). Western blot analyses revealed upregulation of Akt-eNOS-NO-cGMP-GS3Kβ signaling early in the progression of hypertrophy and heart failure. We also observed significant reductions in myocardial fibrosis coupled with increases in myocardial vascularity suggesting an NO-mediated pro-angiogenic response in nitrite treated animals.
Conclusions: These results demonstrate that sodium nitrite significantly increases Akt-eNOS-NO-cGMP signaling, promotes myocardial angiogenesis, and significantly preserves left ventricular function during pressure-overload induced heart failure.
- © 2013 by American Heart Association, Inc.