Sex difference in nitric oxide synthase-dependent dilatation of cerebral arterioles during long-term alcohol consumption

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Background: Although long-term alcohol consumption impairs both endothelial nitric oxide synthase (NOS) (eNOS)-dependent and neuronal NOS (nNOS)-dependent reactivity of cerebral arterioles in male rats, the influence of sex on alcohol consumption-induced impairment of NOS-dependent cerebral vasodilation has not been examined. Therefore, the authors' first goal was to determine whether long-term alcohol consumption alters eNOS-dependent and nNOS-dependent reactivity of pial arterioles in female rats. Their second goal was to examine potential mechanisms for impaired responses of pial arterioles during long-term alcohol consumption. Methods: Male and female rats were fed liquid diets with or without alcohol for 2-3 months. The authors measured the in vivo diameter of pial arterioles in response to eNOS-dependent agonists (acetylcholine and ADP), nNOS-dependent agonists (kainate and NMDA), and NOS-independent agonists (nitroglycerin and diethylaminodiazen (NONOate)) in the absence and presence of tetrahydrobiopterin (BH4). Results: Topical application of acetylcholine (1.0 and 10 μM), ADP (10 and 100 μM), kainate (100 and 300 μM), and NMDA (100 and 300 μM) produced dose-related dilatation of pial arterioles. However, the magnitude of vasodilation in response to acetylcholine and ADP was significantly less in alcohol-fed male and female rats, and the magnitude of vasodilation in response to kainate and NMDA was significantly less in alcohol-fed male rats. Nitroglycerin and NONOate produced similar vasodilation in non-alcohol-fed and alcohol-fed male and female rats. Application of BH4 did not alter vasodilation in non-alcohol-fed rats but improved impaired eNOS-dependent vasodilation in alcohol-fed male and female rats. Conclusions: Our findings suggest that long-term alcohol consumption impairs eNOS-dependent but not nNOS-dependent dilatation of cerebral arterioles in female rats and that impaired eNOS-dependent vasodilation may be related to a deficiency or alteration in the utilization of BH4.

Original languageEnglish (US)
Pages (from-to)430-436
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Issue number3
Publication statusPublished - Mar 1 2005



  • Alcohol
  • Brain
  • Nitric Oxide Synthase
  • Sex
  • Stroke

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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