ONTOGENY OF NO ACTIVITY AND RESPONSE TO INHALED NO IN THE DEVELOPING OVINE PULMONARY CIRCULATION

To determine maturation-related changes in nitric oxide (NO) activity in the developing pulmonary circulation, we studied the hemodynamic ef fects of endogenous NO inhibition under basal conditions in the premat ure ovine fetus and the response to birth-related stimuli and exogenou s NO in 30 fetal sheep at three different gestational ages. At 0.95 te rm, pulmonary vasodilation during inhaled NO (20 parts per million) wa s equivalent to the dilator response to 100% O-2, but at 0.86 term vas odilation during inhaled NO was greater than the dilator response to 1 00% O-2 (P < 0.05). At 0.78 term, left pulmonary arterial flow (Q(LPA) ) did not increase with exposure to either NO or 100% O-2. Intrapulmon ary infusion of nitro-L-arginine (L-NA) increased basal pulmonary vasc ular resistance 38% in the premature fetus at 0.78 term. L-NA treatmen t decreased the ventilation-induced rise in Q(LPA) by 60% compared wit h controls (P < 0.05). Inhaled NO but not 100% O-2 increased Q(LPA) af ter L-NA treatment to levels achieved with ventilation alone in the co ntrols. We conclude that in the premature pulmonary circulation (0.78 term) 1) basal pulmonary vascular resistance is modulated by endogenou s NO, 2) pulmonary vasodilation at birth is partly mediated by endogen ous NO activity, and 3) inhaled NO causes potent vasodilation.