Published Online
on July 13, 2009

A more recent version of this article appeared on September 1, 2009

This Article Full Text (PDF) Data Supplement All Versions of this Article: 54/3/668    most recent HYPERTENSIONAHA.109.133397v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Csiszar, A. Articles by Ungvari, Z. PubMed PubMed Citation Articles by Csiszar, A. Articles by Ungvari, Z. Related Collections Pulmonary circulation and disease Endothelium/vascular type/nitric oxide Related Article

Submitted on March 25, 2009
Revised on April 21, 2009

Resveratrol Prevents Monocrotaline-Induced Pulmonary Hypertension in Rats

Anna Csiszar; Nazar Labinskyy; Susan Olson; John T. Pinto; Sachin Gupte; Joseph M. Wu; Furong Hu; Praveen Ballabh; Andrej Podlutsky; Gyorgy Losonczy; Rafael de Cabo; Rajamma Mathew; Michael S. Wolin; and Zoltan Ungvari^*

From the Departments of Physiology (A.C., N.L., M.S.W., Z.U.), Anatomy and Cell Biology (F.H., P.B., R.M.), and Pediatrics (F.H., P.B., R.M.), New York Medical College, Valhalla, NY; Reynolds Oklahoma Center on Aging (A.C., Z.U.), Department of Geriatric Medicine, University of Oklahoma Health Science Center, Oklahoma City, Okla; Department of Biochemistry (S.O., J.T.P., J.M.W.), New York Medical College-Westchester Medical Center, Valhalla, NY; Department of Biochemistry and Molecular Biology (S.G.), University of South Alabama, Mobile, Ala; Sam and Ann Barshop Institute for Longevity and Aging Studies (A.P.), University of Texas Health Science Center, San Antonio, Tex; Department of Pulmonology (G.L., Z.U.), Semmelweis University, Budapest, Hungary; Laboratory of Experimental Gerontology (R.d.C.), National Institute on Aging, Baltimore, Md.

^* To whom correspondence should be addressed. E-mail: ungzol{at}yahoo.com.

Abstract—Proliferation of pulmonary arterial smooth muscle cells, endothelial dysfunction, oxidative stress, and inflammation promotes the development of pulmonary hypertension. Resveratrol is a polyphenolic compound that exerts antioxidant and anti-inflammatory protective effects in the systemic circulation, but its effects on pulmonary arteries remain poorly defined. The present study was undertaken to investigate the efficacy of resveratrol to prevent pulmonary hypertension. Rats injected with monocrotaline progressively developed pulmonary hypertension. Resveratrol treatment (25 mg/kg per day, PO, from day 1 postmonocrotaline) attenuated right ventricular systolic pressure and pulmonary arterial remodeling, decreased expression of inflammatory cytokines (tumor necrosis factor-, interleukin 1, interleukin 6, and platelet-derived growth factor-/), and limited leukocyte infiltration in the lung. Resveratrol also inhibited proliferation of pulmonary arterial smooth muscle cells. Treatment of rats with resveratrol increased expression of endothelial NO synthase, decreased oxidative stress, and improved endothelial function in small pulmonary arteries. Pulmonary hypertension was associated with an upregulation of NAD(P)H oxidase in small pulmonary arteries, which was significantly attenuated by resveratrol treatment. Our studies show that resveratrol exerts anti-inflammatory, antioxidant, and antiproliferative effects in the pulmonary arteries, which may contribute to the prevention of pulmonary hypertension.

Key words: pulmonary hypertension • resveratrol • oxidative stress • endothelial dysfunction • inflammation

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Is Resveratrol the Magic Bullet for Pulmonary Hypertension?

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