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 sensitiv e to both acute changes in oxygen levels (in vitro) and chronic changes (in utero). STUDY DESIGN: Pregnant guinea pigs near term were exposed to either normoxi a or hypoxia (12% oxygen) for 4 or 7 days. The effect of decreasing PO2 in vitro (acute hypoxia) on relaxation in response to acetylcholine, A23187, s odium nitroprusside, and 8-bromo-cyclic guanosine monophosphate was measure d in isolated carotid arteries from normoxic fetuses. In separate experimen ts relaxation in response to acetylcholine and sodium nitroprusside of endo thelially intact and denuded fetal arteries from fetuses exposed to normoxi c conditions and long-term (4 and 7 days) hypoxic conditions was measured i n the presence and absence of nitro-L-arginine (10(-4) mol/L). RESULTS: Acute hypoxia inhibited endothelium-dependent relaxation in respon se to acetylcholine and A23187, increased sensitivity to sodium nitroprussi de, but had no effect on relaxation in response to 8-bromo-cyclic guanosine monophosphate. Chronic hypoxia (4 but not 7 days) inhibited maximal relaxa tion of arteries in response to acetylcholine but not relaxation of arterie s in response to sodium nitroprusside with respect to relaxation seen in ar teries from normoxic fetuses. Nitro-L-arginine attenuated the differences b etween normoxic and hypoxic fetuses in acetylcholine response. CONCLUSION: Hypoxia may alter relaxation of fetal arteries by decreasing th e availability of oxygen for nitric oxide production and causing vascular a daptations related to altered nitric oxide release.