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Regulation of alveolar gas conductance by NO in man, as based on studies with NO donors and inhibitors of NO production
Author(s) -
Guazzi M.,
Arena R.,
Vicenzi M.,
Guazzi M. D.
Publication year - 2009
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2008.01939.x
Subject(s) - pulmonary artery , dlco , nitric oxide , saline , vascular resistance , omega n methylarginine , lung , chemistry , medicine , endocrinology , hemodynamics , diffusing capacity , nitric oxide synthase , lung function
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 min 1 ) 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.