THE EFFECT OF N-OMEGA-NITRO-L-ARGININE METHYLESTER ON HYPOXIC VASOCONSTRICTION IN THE NEONATAL PIG LUNG

This study was carried out to determine the influence and site of acti on of N(omega)-nitro-L-arginine methylester, an L-arginine analogue, o n basal pulmonary vascular tone and hypoxic vasoconstriction in neonat al pig lungs. We studied isolated lungs from pigs, age 14.5 +/- 0.5 (S D) d and weight 3.6 +/- 0.7 kg, perfused with autologous blood at a co nstant flow rate. The arterial-venous occlusion method was used to det ermine sites of action upstream and downstream of the double occlusion pressure (Pd) during baseline, infusion of acetylcholine, and ventila tion of the lung with a hypoxic gas mixture. The measurements were the n repeated during the three conditions described above after adding N( omega)-nitro-L-arginine methylester, a competitive inhibitor of nitric oxide synthase, to the blood. During control conditions, the vascular resistance was almost evenly divided upstream and downstream of Pd. I nfusion of acetylcholine resulted in downstream dilation, and hypoxia resulted in an increase in both upstream and downstream resistance. Af ter adding N(omega)-nitro-L-arginine methylester to the blood, there w as an increase in both upstream and downstream resistances; acetylchol ine infusion resulted in an increase in total vascular resistance, whi ch was entirely due to upstream constriction; and the hypoxia response was much larger both upstream and downstream of Pd. These results sug gest that nitric oxide synthase helped maintain a low level of basal p ulmonary vascular tone both upstream and downstream of Pd in these neo natal pig lungs; that the vascular effect of acetylcholine was changed from downstream dilation to upstream constriction by N(omega)-nitro-L -arginine methylester, and that nitric oxide synthase activity modulat ed both the upstream and downstream vasomotor response to hypoxia.