EDRF IN PULMONARY RESISTANCE VESSELS FROM FETAL LAMB - STIMULATION BYOXYGEN AND BRADYKININ

Endothelium-derived relaxing factor-nitric oxide (EDRF-NO) has been st udied in isolated, pulmonary resistance vessels from term fetal lambs at a fetal (21 +/- 0.2 mmHg) and neonatal (69 +/- 0.4 mmHg) Po-2. Brad ykinin dose dependently (0.1-100 nM) relaxed arteries and veins that h ad been precontracted with a thromboxane A(2) analogue. Their response did not differ at low Po-2, whereas the response of the arteries was greater at high Po-2. Sodium nitroprusside was almost as potent as bra dykinin on the arteries, but its action did not vary with Po-2. Acetyl choline also relaxed the arteries at higher concentrations (0.1-100 mu M). N-omega-monomethyl-L-arginine (L-NMMA) and N-omega-nitro-L-argini ne methyl ester (L-NAME) (both at 100 mu M) weakly contracted arteries at low Po-2. The contraction to L-NAME, but not L-NMMA, increased wit h the Po-2. In the arteries, L-NAME had no effect on bradykinin relaxa tion at low Po-2, whereas it was an inhibitor at high Po-2. Conversely , L-NMMA slightly inhibited bradykinin relaxation regardless of Po-2. In the veins, L-NAME transiently increased basal tone and inhibited br adykinin relaxation at either Po-2 Indomethacin (2.8 mu M) had no effe ct on arteries at low Po-2, whereas it was a constrictor at high Po-2. No indomethacin constriction occurred in the veins. We conclude that fetal pulmonary resistance vessels possess an EDRF-NO relaxing mechani sm that is stimulated by bradykinin. In the arteries, this mechanism i s more effective at high Po-2. A prostaglandin relaxing mechanism is a lso activated by oxygen in the arteries. These relaxing agents are lik ely important for the adjustment of the pulmonary circulation at birth .