Regulation of alveolar gas conductance by NO in man, as based on studies with NO donors and inhibitors of NO production.

Aim: Nitric oxide (NO) is a mediator of the pulmonary vessel tone and permeability. We hypothesized that it may also regulate the alveolar-capillary membrane gas conductance and lung diffusion capacity. Methods: In 20 healthy subjects (age = 23 ± 3 years) we measured lung diffusion capacity for carbon monoxide (DLco), its determinants (membrane conductance, D m , and pulmonary capillary blood volume, V c ), systolic pulmonary artery pressure (PAPs) and pulmonary vascular resistance (PVR). Measurements were performed before and after administration of N G -monomethyl-L-arginine (L-NMMA, 0.5 mg kg -1 min -1 ), as a NO production inhibitor, and L-arginine (L-Arg, 0.5 mg kg -1 mini) as a NO pathway activator. The effects of L-NMMA were also tested in combination with active L-Arg and inactive stereoisomer D-Arg vehicled by 150 mL of 5% D-glucose solution. For L-Arg and L-NMMA, saline (150 mL) was also tested as a vehicle. Results: L-NMMA reduced D m (-41% P < 0.01), DLco (-20%, P < 0.01) and cardiac output (CO), and increased PAPs and PVR. In 10 additional subjects, a dose of L-NMMA of 0.03 mg kg -1 min 1 infused in the main stem of the pulmonary artery was able to lower D m (-32%, P < 0.01) despite no effect on PVR and CO. D m depression was significantly greater when L-NMMA was vehicled by saline than by glucose. L-Arg but not D-Arg abolished the effects of L-NMMA. L-Arg alone increased D m (+14%, P < 0.01). Conclusion: The findings indicate that NO mediates the respiratory effects of L-NMMA and L-Arg, and is involved in the physiology of the alveolar-capillary membrane gas conductance in humans. NO deficiency may cause an excessive endothelial sodium exchange/water conduction and fluid leakage in alveolar interstitial space, lengthening the air-blood path and depressing diffusion capacity.