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Inhibition of Endothelin‐1 Receptors Improves Impaired Nitric Oxide Synthase‐Dependent Dilation of Cerebral Arterioles in Type‐1 Diabetic Rats
Author(s) -
ARRICK DENISE M.,
MAYHAN WILLIAM G.
Publication year - 2010
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2010.00042.x
Subject(s) - medicine , endocrinology , enos , nitric oxide synthase , nitric oxide , vasodilation , endothelin receptor , diabetes mellitus , receptor , chemistry
Please cite this paper as: Arrick and Mayhan (2010). Inhibition of Endothelin‐1 Receptors Improves Impaired Nitric Oxide Synthase‐Dependent Dilation of Cerebral Arterioles in Type‐1 Diabetic Rats. Microcirculation 17(6) , 439–446. Abstract Objective: Endothelin‐1 has been implicated in the pathogenesis of many cardiovascular‐related diseases, including diabetes. The goal of this study was to examine the influence of endothelin‐1 receptors (ET A ) in impaired responses of cerebral (pial) arterioles in type‐1 diabetic rats. Methods: We measured responses of cerebral arterioles in non‐diabetic rats to endothelial nitric oxide synthase (eNOS)‐dependent (ADP), neuronal nitric oxide synthase (nNOS)‐dependent ( N ‐methyl‐ d ‐aspartic acid [NMDA]) and NOS‐independent (nitroglycerin) agonists before and during application of BQ‐123, an ET A receptor antagonist. In addition, we harvested brain tissue from non‐diabetic and diabetic rats to measure the production of superoxide anion under basal conditions and during inhibition of ET A receptors. Results: We found that diabetes specifically impaired eNOS‐ and nNOS‐dependent reactivity of cerebral arterioles, but did not alter NOS‐independent vasodilation. In addition, while BQ‐123 did not alter responses in non‐diabetic rats, BQ‐123 restored impaired eNOS‐ and nNOS‐dependent vasodilation in diabetic rats. Further, superoxide production was higher in brain tissue from diabetic rats compared with non‐diabetic rats under basal conditions and BQ‐123 decreased basal production of superoxide in diabetic rats. Conclusion: We suggest that activation of ET A receptors during type‐1 diabetes mellitus plays an important role in impaired eNOS‐ and nNOS‐dependent dilation of cerebral arterioles.