Losartan improves impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type 1 diabetic rats

Denise M. Arrick, Glenda M. Sharpe, Hong Sun, William G. Mayhan

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We examined whether activation of angiotensin-1 receptors (AT1R) could account for impaired responses of cerebral arterioles during type 1 diabetes (T1D). First, we measured responses of cerebral arterioles in nondiabetic rats to eNOS-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists before and during application of angiotensin II. Next, we examined whether losartan could improve impaired responses of cerebral arterioles during T1D. In addition, we harvested cerebral microvessels for Western blot analysis of AT1R protein and measured production of superoxide anion by brain tissue under basal conditions and in response to angiotensin II in the absence or presence of losartan. We found that angiotensin II specifically impaired eNOS-dependent reactivity of cerebral arterioles. In addition, while losartan did not alter responses in nondiabetics, losartan restored impaired eNOS-dependent vasodilatation in diabetics. Further, AT1R protein was higher in diabetics compared to nondiabetics. Finally, superoxide production was higher in brain tissue from diabetics compared to nondiabetics under basal conditions, angiotensin II increased superoxide production in nondiabetics and diabetics, and losartan decreased basal (diabetics) and angiotensin II-induced production of superoxide (nondiabetics and diabetics). We suggest that activation of AT1R during T1D plays a critical role in impaired eNOS-dependent dilatation of cerebral arterioles.

Original languageEnglish (US)
Pages (from-to)128-135
Number of pages8
JournalBrain Research
Volume1209
DOIs
StatePublished - May 13 2008

Keywords

  • ADP
  • Acetylcholine
  • Angiotensin II
  • Brain
  • Nitroglycerin
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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