Hemodynamic effects of basal and stimulated release of endogenous nitric oxide in isolated human lungs.

Background-We compared the hemodynamic responses to inhibition or stimulation of endothelial nitric oxide (NO) release of isolated explanted lungs from transplantation recipients with pulmonary hypertension and in normotensive unallocated donor lungs. Methods and Results-Lungs from 10 patients with severe pulmonary hypertension (SPH) and from 16 patients with severe chronic obstructive lung disease (COLD) were studied. Fourteen normotensive lungs were studied as controls. The lungs were perfused at a constant flow. In protocol 1 N(G)-nitro-L-arginine methyl ester caused a similar rise in baseline pulmonary artery pressure (PAP) that was similar in SPH (+17.1+/-4.2 mm Hg; n=5), COLD (+15.5+/-4.8 mm Hg; n=8), and control lungs (+14.5+/-1.5 mm Hg; n=7). Arterial occlusion demonstrated that most of the changes with N(G)-nitro-L-arginine methyl ester were precapillary. The response to sodium nitroprusside (10(-8) to 10(-4) mol/L) was similar in all groups. In protocol 2, the lungs were preconstricted, and acetylcholine (10(-9) to 10(-5) mol/L) caused a lesser fall in PAP in both COLD and SPH lungs compared with control (-41.9+/-8.6%, -55. 7+/-7.6%, and -73.2+/-2.5%, respectively; P<0.05), whereas sodium nitroprusside (10(-5) mol/L) decreased PAP to initial levels in all lungs. Conclusions-Stimulated release of NO is impaired in arteries of lungs with plexogenic or hypoxemic pulmonary hypertension. In contrast, basal release of NO appears to be maintained.