Original ArticleNitrite Prevents Right Ventricular Failure and Remodeling Induced by Pulmonary Artery BandingHu, Jian MD, PhD*; Sharifi-Sanjani, Maryam PhD*; Tofovic, Stevan P. MD, PhD*,†Author Information *Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA; and †Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA. Reprints: Jian Hu, MD, PhD, Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15216 (e-mail: [email protected]). Partially supported by NIH grant “P01 HL103455-06.” The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcvp.org). Journal of Cardiovascular Pharmacology: February 2017 - Volume 69 - Issue 2 - p 93-100 doi: 10.1097/FJC.0000000000000446 Buy SDC Metrics Abstract Background: Nitrite has been shown to reduce right ventricle (RV) remodeling in experimental pulmonary hypertension. However, whether this effect is due to a reduction in RV afterload (ie, reduction in pulmonary artery pressure) or a direct effect on the RV itself remains unanswered. We hypothesize that nitrite has direct effects on RV remodeling and studied its effects in mice with pulmonary artery banding (PAB). Methods and Results: PAB decreased exercise tolerance and reduced RV systolic and diastolic function. Nitrite treatment attenuated the decrease in RV systolic function and improved the RV diastolic function. Nitrite-treated mice with PAB had similar exercise tolerance compared with a control group. PAB induced RV hypertrophy and fibrosis which were associated with increased expression of phospho-Akt. Interestingly, nitrite treatment attenuated PAB-induced RV hypertrophy and reduced the expression of phospho-Akt in RV tissue from mice with PAB. In neonatal rat cardiac fibroblast, nitrite also attenuated hypoxia-induced increase in expression of phospho-Akt. Conclusion: Our study indicates that nitrite treatment has direct beneficial effects on RV and improves function and attenuates remodeling in RV exposed to chronic pressure overload. These beneficial effects, at least in part, could be due to the inhibition of the phospho-Akt (p-Akt) pathway activation. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.