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

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Abstract:

Abstract 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, Dm, and pulmonary capillary blood volume, Vc), systolic pulmonary artery pressure (PAPs) and pulmonary vascular resistance (PVR). Measurements were performed before and after administration of Ng-monomethyl-l-arginine (l-NMMA, 0.5 mg kg−1 min−1), as a NO production inhibitor, andl-arginine (l-Arg, 0.5 mg kg−1 min1) as a NO pathway activator. The effects ofl-NMMA were also tested in combination with activel-Arg and inactive stereoisomerd-Arg vehicled by 150 mL of 5%d-glucose solution. Forl-Arg andl-NMMA, saline (150 mL) was also tested as a vehicle. Results: 

l-NMMA reduced Dm (−41%P < 0.01), DLco (−20%, P < 0.01) and cardiac output (CO), and increased PAPs and PVR. In 10 additional subjects, a dose ofl-NMMA of 0.03 mg kg−1 min1 infused in the main stem of the pulmonary artery was able to lower Dm (−32%, P < 0.01) despite no effect on PVR and CO. Dm depression was significantly greater whenl-NMMA was vehicled by saline than by glucose.l-Arg but notd-Arg abolished the effects ofl-NMMA.l-Arg alone increased Dm (+14%, P < 0.01). Conclusion: 

The findings indicate that NO mediates the respiratory effects ofl-NMMA andl-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.

Keywords: gas diffusion; nitric oxide; pulmonary circulation

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1748-1716.2008.01939.x

Affiliations: 1:  Cardiopulmonary Unit, University of Milan, San Paolo Hospital, Milan, Italy 2:  Virginia Commonwealth University, Richmond, VA, USA 3:  Institute of Cardiology, University of Milan, Milan, Italy

Publication date: June 1, 2009

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