Korean Circ J.  2006 Oct;36(10):683-687. 10.4070/kcj.2006.36.10.683.

Resveratrol Attenuates Monocrotaline-Induced Pulmonary Hypertension in Rats

• Lee DS
• Jung JY
• Jung YW

• KMID: 2029030
• DOI: http://doi.org/10.4070/kcj.2006.36.10.683

Abstract

BACKGROUND AND OBJECTIVES
: Resveratrol (RVT) is a polyphenolic phytoalexin, and it has been demonstrated to be capable of protecting against cardiovascular disease. The aim of this study was to identify whether RVT might protect against monocrotaline (MCT)-induced pulmonary hypertension and whether vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) are involved in the beneficial effects.
MATERIALS AND METHODS
: Thirty Sprague Dawley rats were divided into three groups: the control (n=6), the MCT (n=12) and the MCT with RVT (5 mg/kg/day, n=12) groups. After 28 days, the tissue samples were obtained for morphometric analysis and Western blotting.
RESULTS
: In the MCT group, the right ventricle/(left ventricle+septum) weight ratio was significantly increased compared with that of the control group (0.51+/-0.07 vs. 0.20+/-0.03, p<0.01), which was markedly suppressed in the RVT treated group (0.35+/-0.08, p<0.01). Histological analysis also showed that MCT treatment increased the medial wall thickness of the pulmonary arterioles compared with that of the control group (36+/-8% vs. 17+/-5%, p<0.01), which also was significantly suppressed in the RVT treated group (27+/-5%, p<0.01). In addition, Western blot demonstrated the decreased expression of VEGF in the MCT group (p<0.01), which was upregulated after long term RVT treatment (p<0.01). The expression of eNOS was increased after MCT treatment (p<0.01), but upregulation of eNOS could not be reversed by the RVT treatment. The expression of iNOS was not significantly modulated.
CONCLUSION
: These results suggest that RVT attenuates MCT-induced pulmonary hypertension and it may represent a new strategy for the treatment of pulmonary hypertension.

Keyword

Resveratrol; Vascular endothelial growth factor; Endothelial nitric oxide synthase; Pulmonary hypertension

MeSH Terms

Animals
Arterioles
Blotting, Western
Cardiovascular Diseases
Hypertension, Pulmonary*
Monocrotaline
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Rats*
Rats, Sprague-Dawley
Up-Regulation
Vascular Endothelial Growth Factor A
Monocrotaline
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Vascular Endothelial Growth Factor A