Smooth muscle glutathione depletion contributes to increased myogenic tone in resistance arteries of type‐2 diabetic mice

Abstract

Oxidative stress associated with increased reactive oxygen species and depleted levels of antioxidants such as glutathione (GSH) are hallmarks of diabetes. In the present study, we tested the hypothesis that GSH depletion contributes to the increased myogenic tone observed in type‐2 diabetes. Mesenteric arteries isolated from 12–14 week old diabetic (db/db) and nondiabetic (db/m) mice were denuded of endothelium, cannulated, and myogenic tone measured as percentage of a passive vessel diameter. At physiological pressures, myogenic tone was greater in vessels from the db/db compared to db/m. GSH levels were experimentally elevated in db/db vessels by incubating overnight with GSH ethyl ester. Increased GSH levels in the diabetic db/db vessels reduced myogenic tone compared to untreated db/db controls. In the reciprocal experiment, GSH levels in nondiabetic db/m vessels were depleted by overnight treatment with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor. The BSO treated db/m vessels showed increased myogenic tone compared to untreated controls. In conclusion, these data suggest that depletion of the vascular smooth muscle GSH pool contributes to increased myogenic tone in mesenteric vessels from type 2 diabetic animals. Funded by the American Heart Association.