Effects of acute and chronic hypoxia on nitric oxide-mediated relaxation of fetal guinea pig arteries.
OBJECTIVE
These studies tested whether fetal artery reactivity is sensitive to both acute changes in oxygen levels (in vitro) and chronic changes (in utero).


METHODS
Pregnant guinea pigs near term were exposed to either normoxia or hypoxia (12% oxygen) for 4 or 7 days. The effect of decreasing PO (2 ) in vitro (acute hypoxia) on relaxation in response to acetylcholine, A23187, sodium nitroprusside, and 8-bromo-cyclic guanosine monophosphate was measured in isolated carotid arteries from normoxic fetuses. In separate experiments relaxation in response to acetylcholine and sodium nitroprusside of endothelially intact and denuded fetal arteries from fetuses exposed to normoxic conditions and long-term (4 and 7 days) hypoxic conditions was measured in the presence and absence of nitro-L -arginine (10(-4) mol/L).


RESULTS
Acute hypoxia inhibited endothelium-dependent relaxation in response to acetylcholine and A23187, increased sensitivity to sodium nitroprusside, but had no effect on relaxation in response to 8-bromo-cyclic guanosine monophosphate. Chronic hypoxia (4 but not 7 days) inhibited maximal relaxation of arteries in response to acetylcholine but not relaxation of arteries in response to sodium nitroprusside with respect to relaxation seen in arteries from normoxic fetuses. Nitro-L -arginine attenuated the differences between normoxic and hypoxic fetuses in acetylcholine response.


CONCLUSIONS
Hypoxia may alter relaxation of fetal arteries by decreasing the availability of oxygen for nitric oxide production and causing vascular adaptations related to altered nitric oxide release.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
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Thompson
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Weiner
D000109:Acetylcholine; D000208:Acute Disease; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000196:embryology* / Q000503:physiopathology*; D000001:Calcimycin; D002908:Chronic Disease; D006152:Cyclic GMP; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside; D011247:Pregnancy; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000001:Calcimycin; D006152:Cyclic GMP; D000109:Acetylcholine