ROLE OF ENDOTHELIN IN IMPAIRED RESPONSES OF CEREBRAL ARTERIOLES DURING TYPE 1 DIABETES MELLITUS

Abstract

Previous studies have suggested that endothelin‐1 may contribute to vascular abnormalities during a variety of disease states, including Type 1 diabetes mellitus. Endothelin‐1 may contribute to structural and functional abnormalities of the blood vessels, and may also regulate the expression of other growth factors and cytokines to influence vascular function. However, there is a lack of information regarding the precise role of endothelin‐1 in altered NOS‐dependent responses of cerebral arterioles during Type 1 diabetes. Thus, our goal was to determine whether acute inhibition of endothelin‐1 receptors (BQ‐123) could influence NOS‐dependent responses of cerebral arterioles in diabetic rats. We measured diameter of pial arterioles in nondiabetic and diabetic (STZ; 50 mg/kg) rats in response to eNOS‐ and nNOS‐dependent (ADP and NMDA) and ‐independent (nitroglycerin) agonists before and during treatment with BQ‐123. In addition, we measured superoxide production by cerebral cortex tissue obtained from nondiabetic and diabetic rats. We found that eNOS‐ and nNOS‐dependent dilation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, treatment with BQ‐123 restored impaired responses of cerebral arterioles in diabetic rats towards that observed in nondiabetic rats. Further the production of superoxide anion by cortex tissue was increased in diabetic rats when compared to nondiabetic rats. We suggest that endothelin‐1 may contribute to impaired responses of cerebral arterioles during Type 1 diabetes. We speculate that endothelin receptor antagonism may be a potential therapeutic tool for the treatment of cerebrovascular dysfunction observed in diabetic subjects.