Inhibition of endothelin-1 receptors improves impaired nitric oxide synthase-dependent dilation of cerebral arterioles in type-1 diabetic rats

Denise M. Arrick, William G. Mayhan

Research output: Contribution to journalArticle

17 Scopus citations

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 (ETA) 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 ETA 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 ETA receptors during type-1 diabetes mellitus plays an important role in impaired eNOS- and nNOS-dependent dilation of cerebral arterioles.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalMicrocirculation
Volume17
Issue number6
DOIs
StatePublished - Aug 2010

Keywords

  • ADP
  • NMDA
  • brain
  • nitroglycerin
  • oxidative stress
  • superoxide anion

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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