Denise M Arrick1, William G Mayhan. 1. Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
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.
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 diabeticrats. METHODS: We measured responses of cerebral arterioles in non-diabeticrats 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 diabeticrats 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-diabeticrats, BQ-123 restored impaired eNOS- and nNOS-dependent vasodilation in diabeticrats. Further, superoxide production was higher in brain tissue from diabeticrats compared with non-diabeticrats under basal conditions and BQ-123 decreased basal production of superoxide in diabeticrats. 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.
Authors: Aaron S Dumont; Randall J Dumont; John H McNeill; Neal F Kassell; Garnette R Sutherland; Subodh Verma Journal: Neurosurgery Date: 2003-03 Impact factor: 4.654
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