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

Background-We compared the hemodynamic responses to inhibition or stimulati on of endothelial nitric oxide (NO) release of isolated explanted lungs fro m transplantation recipients with pulmonary hypertension and in normotensiv e unallocated donor lungs. Methods and Results-Lungs from 10 patients with severe pulmonary hypertensi on (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-argin ine methyl ester caused a similar rise in baseline pulmonary artery pressur e (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 occlus ion demonstrated that most of the changes with NG-nitro-L-arginine methyl e ster 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 precons tricted, 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 nitroprussi de (10(-5) mom) 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.