Effect of inhibitors of nitric oxide release and action on vascular tone in isolated lungs of pig, sheep, dog and man.

1. The actions of inhibitors of the release or action of nitric oxide (NO) on pulmonary vascular resistance (PVR) were investigated in lungs isolated from pig, sheep, dog and man. 2. In pig, sheep and human lungs perfused with Krebs-dextran solution, both N omega-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) and Methylene Blue (10(-4) M) increased basal PVR. This increase was reversed by sodium nitroprusside (10(-5) M). In pig lungs N omega-monomethyl-L-arginine (10(-4) M) increased PVR by 154%. This increase was partially reversed by L-arginine (10(-3) M). L-NAME had no effect in dog lungs. 3. Pulmonary artery pressure-flow (PPA/Q) relationships were studied over a wide range of flows. In pigs, sheep and human lungs perfused with Krebs-dextran solution, L-NAME increased the PPA/Q slope. This increase was reversed by sodium nitroprusside. In dog lungs L-NAME had no effect. 4. In blood-perfused lungs, the respective responses to L-NAME were similar to those observed with saline. Acute hypoxia in pig and dog lungs increased intercept pressure. Addition of L-NAME during hypoxia increased the PPA/Q slope in both species. 5. In the human, there was no difference in the absolute increase of PVR or PPA/Q slope elicited by L-NAME between hypertensive and control lungs. 6. We conclude that NO is continuously released in the pulmonary vascular bed of pig, sheep and humans under normoxic conditions. In dog lungs inhibition of NO synthesis increases PVR only under hypoxic conditions. In human lungs with pulmonary hypertension, NO is still released under basal conditions.