Insulin reverses impaired acetylcholine-induced dilatation of the rat basilar artery during diabetes mellitus

William G. Mayhan, Anna K. Trauernicht, Scott D. Irvine

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The goal of this study was to determine whether treatment of diabetic rats with insulin reverses impaired nitric oxide synthase-dependent reactivity of the basilar artery in vivo. We measured the diameter of the basilar artery in non-diabetic rats, diabetic (streptozotocin; 50-60 mg/kg i.p.) rats, and diabetic rats treated with insulin implants in response to acetylcholine and nitroglycerin before and following topical application of NG-monomethyl-L-arginine (L-NMMA). Reactivity of the basilar artery was measured 2-3 months after injection of streptozotocin. We found that topical application of acetylcholine (1.0 and 10 μM) produced dose-related dilatation of the basilar artery in non-diabetic rats, which was inhibited (>80%) by topical application of L-NMMA (10 μM). In diabetic rats, the magnitude of vasodilation produced by acetylcholine was significantly less than in non-diabetic rats. Further, topical application of L-NMMA did not affect dilatation of the basilar artery in diabetic rats in response to acetylcholine. In insulin treated diabetic rats, dilatation of the basilar artery in response to acetylcholine was significantly greater than that observed in either non-diabetic or diabetic rats. In contrast, dilatation of the basilar artery in response to nitroglycerin was similar in insulin treated diabetic rats, non-diabetic rats and diabetic rats. Topical application of L-NMMA only partially inhibited dilatation of the basilar artery in response to acetylcholine in diabetic rats treated with insulin. Thus, the findings of this study suggest that impaired acetylcholine-induced dilatation of the basilar artery during diabetes mellitus can be restored by treatment with insulin. Further, it appears that the contribution of cellular pathways, in addition to nitric oxide synthase, may contribute to dilatation of the basilar artery in response to acetylcholine in rats treated with insulin.

Original languageEnglish (US)
Pages (from-to)195-201
Number of pages7
JournalBrain Research
Volume893
Issue number1-2
DOIs
StatePublished - Mar 2 2001

Keywords

  • Acetylcholine
  • Brain
  • Insulin
  • N-monomethyl-L-arginine (L-NMMA)
  • Nitric oxide
  • Nitroglycerin
  • Rat

ASJC Scopus subject areas

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

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