PERINATAL REGULATION OF THE CEREBRAL-CIRCULATION - ROLE OF NITRIC-OXIDE AND PROSTAGLANDINS

Nitric oxide (NO) influences cerebral vascular tone both in the normal fetus and in the hypoxemic fetus, but during postnatal life this regu lating role of NO seems less prominent. It is therefore possible that under conditions when arterial oxygen content is at postnatal levels N O 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 ad ditional fetuses were pretreated with indomethacin to investigate a po ssible additional regulatory role of prostaglandins on cerebral vascul ar resistance. Cerebral blood flow (Q(brain)) was measured using radio nuclide-labeled microspheres. A tracheal tube was inserted to ventilat e the fetus. After recovery, Q(brain) and resistance in the cerebral v ascular bed (R-cer) were measured during the following subsequent cond itions: before and after increasing fetal arterial O-2 content by vent ilation with air, after inhibition of NO production with N-omega-nitro -L-arginine during and after cessation of ventilation, and finally aft er infusion of L-arginine to increase nitric oxide production. Ventila tion decreased Q(brain) (95 +/- 18 to 47 +/- 15 mL/100 g/min) and incr eased R-cer. N-omega-Nitro-L-arginine did not alter Q(brain) (52 +/- 1 3 mL/100 g/min) or R-cer during ventilation and oxygenation, indicatin g no modulating role of NO during higher arterial oxygen content. On c essation of ventilation, Po-2 returned to fetal levels and Q(brain) in creased 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 p revented the rise in cerebral blood flow after cessation of ventilatio n and after additional L-arginine infusion (Q(brain), 53 +/- 20 and 52 +/- 4 mL/100 g/min, respectively). These studies indicate that, durin g postnatal levels of arterial oxygen content, NO does not exert an ac tion on smooth muscle cells of the cerebral resistance vessels as it d oes at lower arterial (fetal) oxygen content. They further show that p rostaglandins are important in facilitating the full expression of NO- induced vasodilation.