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Published on: September 15, 2023
Tetrahydrobiopterin and antioxidants reverse the coronary endothelial dysfunction associated with left ventricular
Olivier Malo1, Fanny Desjardins, Jean-François Tanguay
1Research Center, Montreal Heart Institute, Montreal, Quebec, Canada H1T 1C8.
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, BH(4) 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 BH(4) 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 microM (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 BH(4) and antioxidants constitutes an interesting approach for the prevention of endothelial dysfunction in epicardial coronary arteries associated with left ventricular hypertrophy.
