Hydrogen peroxide mediates endothelium-dependent dilation of coronary arterioles in obese rats on low carbohydrate diet.

OBJECTIVE: Endothelium-dependent vasodilation of coronary arterioles is impaired in obese rats and may be improved by a low-carbohydrate diet. The aim of this study is to elucidate the mechanism by which this improvement occurs. METHODS: We used four groups of male Zucker rats: lean and obese on either standard diet or low-carbohydrate diet. Coronary arterioles were cannulated and pressurized for diameter measurements during administration of acetylcholine or sodium nitroprusside or during flow. Real-time PCR was performed to quantify mRNA expression of super-oxide dismutase and catalase. RESULTS: The low-carbohydrate diet significantly increased endothelium-dependent dilation in the obese rats. N-nitro-L-arginine methyl ester and indomethacin reduced responses to flow and acetylcholine in the lean rats without any effect on the obese on either diet. In contrast, tetraethylammonium and catalase blocked flow-dependent and acetylcholine-induced dilation in the obese on either diet while no effect was observed on the lean. The low-carbohydrate diet in the obese significantly up-regulated catalase mRNA expression and slightly increased super-oxide dismutase mRNA levels. CONCLUSIONS: A , improves endothelium-dependent vasodilation of coronary arterioles in obese rats through the production of hydrogen peroxide which acts as a hyperpolarizing factor, independent of nitric oxide and prostacyclin.