Hydrogen Peroxide Mediates Endothelium-Dependent Dilation of Coronary Arterioles in Obese Rats on a Low-Carbohydrate Diet

ObjectiveEndothelium-dependent vasodilation of coronary arterioles is impaired in obese rats and may be improved by a LCD. The aim of this study is to elucidate the mechanism by which this improvement occurs. MethodsWe used four groups of male Zucker rats: lean and obese on either SD or LCD. 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 CuZnSOD and catalase. ResultsThe LCD significantly increased endothelium-dependent dilation in the obese rats. l-NAME and indomethacin reduced responses to flow and acetylcholine in the lean rats without any effect on the obese on either diet. In contrast, TEA and catalase blocked flow-dependent and acetylcholine-induced dilation in the obese on either diet, while no effect was observed on the lean. The LCD in the obese significantly up-regulated catalase mRNA expression and slightly increased CuZnSOD mRNA levels. ConclusionsA LCD improves endothelium-dependent vasodilation of coronary arterioles in obese rats through the production of H2O2 which acts as a hyperpolarizing factor, independent of nitric oxide and PGI(2).