Glutathione Improves Impaired Responses of Cerebral Arterioles in Type 1 Diabetes

Abstract

Our goal was to examine whether glutathione improves impaired nitric oxide synthase‐dependent responses of cerebral arterioles during Type 1 diabetes. We measured diameter of cerebral arterioles in nondiabetic and diabetic (streptozotocin; 50 mg/kg) rats to nitric oxide synthase‐dependent, acetylcholine and adenosine 5’‐diphosphate (ADP) and a nitric oxide synthase‐independent agonists, nitroglycerin. We measured responses before and during topical application of glutathione (5 mM). In addition, we measured superoxide production by brain tissue in nondiabetic and diabetic rats. In nondiabetic rats, acetylcholine and ADP produced dilatation of cerebral arterioles. However, there was significant impairment in reactivity of arterioles to acetylcholine and ADP in diabetic rats. Vasodilatation to nitroglycerin was similar in nondiabetic and diabetic rats. Glutathione did not alter baseline diameter of cerebral arterioles, but significantly improved impaired nitric oxide synthase‐dependent vasodilatation in diabetic rats. Superoxide production was increased under basal states in diabetic rats and glutathione restored superoxide levels to that observed in nondiabetic rats. Our findings suggest that glutathione selectively improves endothelial dysfunction of cerebral arterioles during Type 1 diabetes.