Perinatal regulation of the cerebral circulation: Role of nitric oxide and prostaglandins

Abstract

Nitric oxide (NO) influences cerebral vascular tone both in the normal fetus and in the hypoxemic fetus, but during postnatal life this regulating role of NO seems less prominent. It is therefore possible that under conditions when arterial oxygen content is at postnatal levels NO exerts no action on smooth muscle. We therefore examined the impact of NO on cerebral blood flow and vascular resistance in five near-term lamb fetuses during intrauterine ventilation and oxygenation. Four additional fetuses were pretreated with indomethacin to investigate a possible additional regulatory role of prostaglandins on cerebral vascular resistance. Cerebral blood flow (Q(brain)) was measured using radionuclide-labeled microspheres. A tracheal tube was inserted to ventilate the fetus. After recovery, Q(brain) and resistance in the cerebral vascular bed (R(ccr)) were measured during the following subsequent conditions: before and after increasing fetal arterial O2 content by ventilation with air, after inhibition of NO production with N(ω)-nitro-L-arginine during and after cessation of ventilation, and finally after infusion of L-arginine to increase nitric oxide production. Ventilation decreased Q(brain) (95 ± 18 to 47 ± 15 mL/100 g/min) and increased R(ccr). N(ω)-Nitro-L-arginine did not alter Q(brain) (52 ± 13 mL/100 g/min) or R(ccr) during ventilation and oxygenation, indicating no modulating role of NO during higher arterial oxygen content. On cessation of ventilation, Po2 returned to fetal levels and Q(brain) increased significantly, but did not return to baseline fetal values (83 ± 7 mL/min). Infusion of L-arginine increased Q(brain) to baseline fetal levels (116 ± 30 mL/min). However, indomethacin pretreatment prevented the rise in cerebral blood flow after cessation of ventilation and after additional L-arginine infusion (Q(brain), 53 ± 20 and 52 ± 4 mL/100 g/min, respectively). These studies indicate that, during postnatal levels of arterial oxygen content. NO does not exert an action off smooth muscle cells of the cerebral resistance vessels as it does at lower arterial (fetal) oxygen content. They further show that prostaglandins are important in facilitating the full expression of NO- induced vasodilation.