Fetal cerebral and peripheral circulatory responses to hypoxia after nitric oxide synthase inhibition

The increase in cerebral blood flow (CBF) during hypoxia in fetal sheep at 0.6 gestation is less than the increase at 0.9 gestation when normalized fo r differences in baseline CBF and oxygen consumption. Nitric oxide (NO) syn thase (NOS) catalytic activity increases threefold during this period of de velopment. We tested the hypothesis that administration of the NOS inhibito r N-omega-nitro-L-arginine methyl ester (L-NAME) decreases the CBF response to systemic hypoxia selectively at 0.9 gestation. We also tested whether a ny peripheral vasoconstriction during hypoxia is potentiated by L-NAME at 0 .9 gestation. Administration of L-NAME increased arterial blood pressure an d decreased microsphere-determined CBF during normoxia in fetal sheep at bo th 0.6 and 0.9 gestation. With subsequent reduction of arterial oxygen cont ent by similar to 50%, the percent increase in forebrain CBF in a control g roup (57 +/- 11%; +/- SE) and L-NAME-treated group (51 +/- 6%) was similar at 0.6 gestation. Likewise, at 0.9 gestation, the increase in CBF was simil ar in control (90 +/- 25%) and L-NAME (80 +/- 28%) groups. At 0.9 gestation , L-NAME treatment attenuated the increase in coronary blood flow and incre ased gastrointestinal vascular resistance during hypoxia. We conclude that NO exerts a basal vasodilatory influence in brain as early as 0.6 gestation in fetal sheep but is not an important mechanism for hypoxic vasodilation in brain at either 0.6 or 0.9 gestation. Thus the developmental increase in NOS catalytic capacity does not appear to be responsible for developmental increases in the CBF response to hypoxia during this period. In contrast, NO modulates the vascular response to hypoxia in heart and gastrointestinal tract.