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, Zoltan Ungvari

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144 Citations (Scopus)

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-α, interleukin 1β, interleukin 6, and platelet-derived growth factor-α/β), 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.

Original languageEnglish
Pages (from-to)668-675
Number of pages8
JournalHypertension
Volume54
Issue number3
DOIs
Publication statusPublished - Sep 1 2009

Keywords

  • Endothelial dysfunction
  • Inflammation
  • Oxidative stress
  • Pulmonary hypertension
  • Resveratrol

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Csiszar, A., Labinskyy, N., Olson, S., Pinto, J. T., Gupte, S., Wu, J. M., Hu, F., Ballabh, P., Podlutsky, A., Losonczy, G., De Cabo, R., Mathew, R., Wolin, M. S., & Ungvari, Z. (2009). Resveratrol prevents monocrotaline-induced pulmonary hypertension in rats. Hypertension, 54(3), 668-675. https://doi.org/10.1161/HYPERTENSIONAHA.109.133397