Effects of binge alcohol exposure in the second trimester on intracerebral arteriolar function in third trimester fetal sheep.
Fetal alcohol syndrome is a leading cause of mental retardation, but mechanisms of alcohol-associated brain damage remain elusive. Chronic alcohol exposure attenuates fetal and neonatal hypoxic cerebral vasodilation in sheep. We therefore hypothesized that alcohol could alter development of cerebrovascular responses to adenosine, a putative mediator of hypoxic cerebral vasodilation. The objective of this study was to examine the effect of earlier fetal alcohol exposure on later reactivity to adenosine in fetal sheep cerebral arterioles. Penetrating intracerebral arterioles were harvested from the brains of third trimester fetal sheep previously exposed in the second trimester to maternal alcohol "binges" (1.5 g/kg IV over 90 min, 5 days/week for 4 weeks) or same-volume saline infusions. Arterioles were cannulated with a micropipette system and luminally pressurized. Fetal alcohol exposure did not affect spontaneous myogenic tone, but enhanced the dilator response of penetrating arterioles to extraluminal acidosis (pH 6.8). Alcohol exposure also resulted in an increase in maximal vessel response to CGS-21680, an adenosine A2A receptor agonist, but did not alter the concentration-dependent response curves to adenosine. Our results suggest that earlier alcohol exposure does not impair the subsequent responsiveness of fetal cerebral arterioles to vasodilator agents. Thus, alteration in cerebral vascular response to hypoxia in fetal sheep may not be attributed to changes in vascular reactivity to adenosine.
Mayock
Dennis E
DE
Division of Neonatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98195-6320, USA. mayock@u.washington.edu
Ngai
Al C
AC
Mondares
Robin L
RL
Gleason
Christine A
CA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D000431:Ethanol; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D010627:Phenethylamines / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D010627:Phenethylamines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000431:Ethanol; D000241:Adenosine