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Cardiovascular Research 2003 59(2):501-511; doi:10.1016/S0008-6363(03)00390-0
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Tetrahydrobiopterin and antioxidants reverse the coronary endothelial dysfunction associated with left ventricular hypertrophy in a porcine model

Olivier Maloa,c, Fanny Desjardinsa,c, Jean-François Tanguaya, Jean-Claude Tardifa, Michel Carrierb and Louis P. Perraultb,c,*

aResearch Center, Montreal Heart Institute, Montreal, Quebec, Canada H1T 1C8
bDepartment of Surgery, Montreal Heart Institute, Montreal, Quebec, Canada H1T 1C8
cDepartment of Pharmacology, Université de Montreal, Canada

* Corresponding author. Tel.: +1-514-376-3330x3471; fax: +1-514-376-1355. lpperrau{at}icm.umontreal.ca

Objective: Endothelium-dependent G-protein mediated relaxations of epicardial coronary arteries is impaired with left ventricular hypertrophy. The objective of this study was to assess the effect of L-arginine, BH4 and the combination of two antioxidants, superoxide dismutase and catalase, on endothelium-dependent relaxations in a swine left ventricular hypertrophy model. Methods: Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed in standard organ chamber experiments to assess the NO pathway in the presence of methyltetrahydropterin (a BH4 analogue), L-arginine, superoxide dismutase and catalase. Results: There was a statistically significant increase in endothelium-dependent relaxation to serotonin and to bradykinin with methyltetrahydropterin and with superoxide dismutase plus catalase (P<0.05) but not with L-arginine compared to untreated coronary arteries from left ventricular hypertrophy animals. Plasma 3-nitrotyrosine level increased significantly from 918±122 to 1844±300 µM (P<0.05 vs. control) after 60 days of aortic banding. Endothelial dysfunction was not associated with a reduced expression of endothelial nitric oxide synthase 2 months after pressure overload left ventricular hypertrophy. Conclusions: Treatment with BH4 and antioxidants constitutes an interesting approach for the prevention of endothelial dysfunction in epicardial coronary arteries associated with left ventricular hypertrophy.

KEYWORDS Antioxidants; Endothelial dysfunction; Left ventricular hypertrophy; Nitric oxide; Tetrahydrobiopterin


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