title: Sex difference in nitric oxide synthase-dependent dilatation of cerebral arterioles during long-term alcohol consumption.
abstract: 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 microM), ADP (10 and 100 microM), kainate (100 and 300 microM), and NMDA (100 and 300 microM) 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.
authors.affiliation: Department of Cellular and Integrative Physiology, 985850 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. hsu1@unmc.edu
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: William G
authors.initials: WG
authors.lastname: Mayhan
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; D014665:Vasodilator Agents; D001708:Biopterins; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C003402:sapropterin