Role of nitric oxide in cerebrovascular reactivity to NMDA and hypercapnia during prenatal development in sheep.
Cerebral vasodilatory responses evoked by activation of NMDA receptors and by hypercapnia are important factors in the integrated vascular response to perinatal cerebral ischemia. Cerebral vasodilation to NMDA is mediated by nitric oxide in adult and newborn animals, whereas vasodilation to hypercapnia is thought to become modulated by nitric oxide, at least in swine, after the newborn period. The developmental role of nitric oxide in the cerebral blood flow response to NMDA and hypercapnia was investigated at mid- and late gestation in fetal sheep. Superfusion of 300microM NMDA over the cerebral cortex through a closed cranial window on the exteriorized head of an anesthetized fetus increased laser-Doppler flow by 41+/-7% (+/-S.E.) at 0.65 gestation. The increase was reduced by superfusion of a nitric oxide synthase inhibitor (18+/-8%). At 0.9 gestation, the response to NMDA was augmented (85+/-24%) compared to that at 0.65 gestation and was reduced by a nitric oxide synthase inhibitor (32+/-6%). In unanesthetized fetal sheep, hypercapnic reactivity of microsphere-determined cerebral blood flow was not significantly attenuated by nitric oxide synthase inhibition at 0.65 gestation (4.6+/-0.7 to 3.7+/-1.0% change/mmHg pCO2) or at 0.9 gestation (4.0+/-0.7 to 3.5+/-0.9% change/mmHg pCO2). Therefore, nitric oxide-dependent cerebrovascular dilation to NMDA-receptor activation is present as early as 0.65 gestation in fetal sheep and increases further during the last trimester, whereas vasodilation to hypercapnia remains unchanged and independent of nitric oxide during the last trimester. Hence, cerebrovascular reactivities to different stimuli do not mature concurrently.
Harris
Andrew P
AP
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Ohata
Hiroto
H
Koehler
Raymond C
RC
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D006935:Hypercapnia / Q000378:metabolism* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D019335:Nitroarginine; D009569:Nitric Oxide; D016202:N-Methylaspartate