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

M. Guazzi, R. Arena, M. Vicenzi, M. D. Guazzi

Research output: Contribution to journalArticle

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, and l-arginine (l-Arg, 0.5 mg kg-1 min1) 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 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 of l-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 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.

Original languageEnglish
Pages (from-to)267-277
Number of pages11
JournalActa Physiologica
Volume196
Issue number2
DOIs
Publication statusPublished - Jun 2009

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Keywords

  • Gas diffusion
  • Nitric oxide
  • Pulmonary circulation

ASJC Scopus subject areas

  • Physiology

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