Abstract 16923: Nitrite Prevents Right Ventricular Failure and Remodeling Induced by Pulmonary Artery Banding
Background: Nitrite has been shown to result in a reduction in RV mass in the condition of pulmonary hypertension. However, whether this effect is due to a simple reduction of RV afterload or a direct effect on the RV remains unanswered. The goal of this study was to determine if oral nitrite treatment could alleviate the remodeling of RV induced by constant RV afterload, thus determining the potential direct effect of the agent on the ventricular myocardium.
Methods: C57BL/6J mice underwent pulmonary artery banding procedure to induce chronic, increased RV afterload. Mice were divided into 2 groups, one (PAB) being treated with regular water and the other (PAB +Nitrite) with NaNO2 in drinking water. Control group did not receive any surgery and was treated with regular water. Acute swimming test was performed after 3 weeks of PAB +/-treatment to evaluate exercise tolerance. Right ventricular hemodynamics was assessed using pressure-volume loop analysis using micromanometry conductance catheterization. Potential mechanism(s) by which nitrite acts was assessed by evaluating the expression of Akt and Calcineurin.
Results: PAB resulted in significantly reduced RV contractility index and exercise tolerance by swimming test as compared to control, while the treatment with nitrite restored the contractility index partially and maintained the exercise tolerance at control level. Nitrite treatment resulted in a marked prevention of the increase in the Fulton index induced by PAB. The expression of Calcineurin decreased significantly in PAB+Nitrite group compared to the PAB one (Calcineurin/βActin: 0.58± 0.08 vs. 1.02± 0.07, p<0.05). The Akt expression in RV tissue had no difference, while the phosphorylated Akt expression is 2.5 times higher in PAB group than PAB+Nitrite group.
Conclusion: Our data suggests that the Nitrite prevents RV remodeling and failure induced by pulmonary hypertension, possibly by preventing the activation of the Calcineurin and p-Akt pathways.
- © 2013 by American Heart Association, Inc.