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Inhibition of endothelin-1 receptors improves impaired nitric oxide synthase-dependent dilation of cerebral arterioles in type-1 diabetic rats.
Arrick, Denise M; Mayhan, William G.
Afiliação
  • Arrick DM; Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
Microcirculation ; 17(6): 439-46, 2010 Aug.
Article em En | MEDLINE | ID: mdl-20690982
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pia-Máter / Vasodilatação / Óxido Nítrico Sintase / Diabetes Mellitus Tipo 1 / Óxido Nítrico Sintase Tipo III / Antagonistas do Receptor de Endotelina A Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pia-Máter / Vasodilatação / Óxido Nítrico Sintase / Diabetes Mellitus Tipo 1 / Óxido Nítrico Sintase Tipo III / Antagonistas do Receptor de Endotelina A Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article