Impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type II diabetic rats

Rose Ann M. Schwaninger, Hong Sun, William G. Mayhan

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The goals of this study were to determine the effects of type II diabetes mellitus on nitric oxide synthase-dependent responses of cerebral arterioles and on endothelial nitric oxide synthase (eNOS) protein in cerebral arterioles. We examined dilatation of cerebral (pial) arterioles in 13-15 week old male lean and diabetic obese Zucker rats in response to nitric oxide synthase-dependent agonists (acetylcholine and adenosine diphosphate (ADP)) and a nitric oxide synthase-independent agonist (nitroglycerin). We found that acetylcholine (10 μM) increased cerebral arteriolar diameter by 10 ± 3% (mean ± SE) in lean Zucker rats, but by only 2 ± 2% in diabetic obese Zucker rats (p < 0.05). In addition, ADP (100 μM) increased cerebral arteriolar diameter by 20 ± 2% in lean Zucker rats, but by only 8 ± 2% in diabetic obese Zucker rats (p < 0.05). In contrast, nitroglycerin produced similar vasodilatation in lean and diabetic obese Zucker rats. Thus, impaired dilatation of cerebral arterioles in diabetic obese Zucker rats is not related to non-specific impairment of vasodilatation. Following these functional studies, we harvested cerebral microvessels for Western blot analysis of eNOS protein. We found that eNOS protein was significantly higher in diabetic obese Zucker rats than in lean Zucker rats (p < 0.05). Thus, type II diabetes mellitus impairs nitric oxide synthase-dependent responses of cerebral arterioles. In addition, eNOS protein from cerebral blood vessels is increased in diabetic obese Zucker rats.

Original languageEnglish (US)
Pages (from-to)3415-3425
Number of pages11
JournalLife Sciences
Volume73
Issue number26
DOIs
StatePublished - Nov 14 2003

Fingerprint

Zucker Rats
Arterioles
Nitric Oxide Synthase
Rats
Dilatation
Nitric Oxide Synthase Type III
Nitroglycerin
Medical problems
Vasodilation
Adenosine Diphosphate
Type 2 Diabetes Mellitus
Proteins
Cholinergic Agonists
Blood vessels
Microvessels
Acetylcholine
Blood Vessels
Western Blotting

Keywords

  • Acetylcholine
  • Adenosine diphosphate
  • Brain
  • Nitric oxide
  • Nitroglycerin
  • Rats
  • Stroke
  • Type II diabetes mellitus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type II diabetic rats. / Schwaninger, Rose Ann M.; Sun, Hong; Mayhan, William G.

In: Life Sciences, Vol. 73, No. 26, 14.11.2003, p. 3415-3425.

Research output: Contribution to journalArticle

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abstract = "The goals of this study were to determine the effects of type II diabetes mellitus on nitric oxide synthase-dependent responses of cerebral arterioles and on endothelial nitric oxide synthase (eNOS) protein in cerebral arterioles. We examined dilatation of cerebral (pial) arterioles in 13-15 week old male lean and diabetic obese Zucker rats in response to nitric oxide synthase-dependent agonists (acetylcholine and adenosine diphosphate (ADP)) and a nitric oxide synthase-independent agonist (nitroglycerin). We found that acetylcholine (10 μM) increased cerebral arteriolar diameter by 10 ± 3{\%} (mean ± SE) in lean Zucker rats, but by only 2 ± 2{\%} in diabetic obese Zucker rats (p < 0.05). In addition, ADP (100 μM) increased cerebral arteriolar diameter by 20 ± 2{\%} in lean Zucker rats, but by only 8 ± 2{\%} in diabetic obese Zucker rats (p < 0.05). In contrast, nitroglycerin produced similar vasodilatation in lean and diabetic obese Zucker rats. Thus, impaired dilatation of cerebral arterioles in diabetic obese Zucker rats is not related to non-specific impairment of vasodilatation. Following these functional studies, we harvested cerebral microvessels for Western blot analysis of eNOS protein. We found that eNOS protein was significantly higher in diabetic obese Zucker rats than in lean Zucker rats (p < 0.05). Thus, type II diabetes mellitus impairs nitric oxide synthase-dependent responses of cerebral arterioles. In addition, eNOS protein from cerebral blood vessels is increased in diabetic obese Zucker rats.",
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