title: Fetal alcohol exposure alters cerebrovascular reactivity to vasoactive intestinal peptide in adult sheep.
abstract: Chronic fetal alcohol exposure impairs neural and vascular development. We have previously shown that fetal alcohol exposure is associated with attenuated hypoxic cerebral vasodilation and reduced neuronal vasoactive intestinal peptide (VIP) expression in fetal sheep. In the present study, we tested the hypothesis that fetal alcohol exposure alters vascular development, leading to altered cerebral vascular reactivity to VIP in adulthood. Penetrating intracerebral arterioles were harvested from the brains of adult (10-13 months old) offspring of ewes that had received intravenous infusions of alcohol (1.5 g/kg) or same-volume saline (90 min/day, 5 days/week) during days 30-82 of gestation (full term = 145 days). The isolated arterioles were cannulated with a micropipette system that allowed luminal perfusion and control of luminal pressure and developed spontaneous tone at 40 degrees C and 60 mm Hg luminal pressure. There was no difference in myogenic tone between arterioles exposed prenatally to alcohol (n = 18) and saline controls (n = 17). However, fetal alcohol exposure significantly (p = 0.03) enhanced the dilator responses of adult intracerebral arterioles to VIP [0.1 nM to 1 microM, logEC(50): -8.6 +/- 0.2 (alcohol) vs. -7.4 +/- 0.8 (saline)]. In contrast, there was no difference in dilator responses to H(+) (pH 6.8 buffer), to adenosine (10 nM to 0.1 mM), or to CGS21680 (an adenosine A(2A) receptor agonist, 0.01 nM to 10 microM). Thus, fetal alcohol exposure alters vasomotor sensitivity to VIP in adult intracerebral arterioles - perhaps a compensatory response to alcohol-induced underdevelopment of neurotransmitter pathways involved in cerebral vascular regulation.
authors.affiliation: Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA 98195-6320, USA.
authors.forename: Al C
authors.initials: AC
authors.lastname: Ngai
authors.forename: Robin L
authors.initials: RL
authors.lastname: Mondares
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Mayock
authors.forename: Christine A
authors.initials: CA
authors.lastname: Gleason
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000502:physiology; D001921:Brain / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000506:poisoning*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D058906:Purinergic P1 Receptor Agonists; D012756:Sheep; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D014665:Vasodilator Agents; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D014660:Vasoactive Intestinal Peptide; D000431:Ethanol; D000241:Adenosine