Association of ex vivo vascular and bronchial dysfunctions in smokers

Oualha, Mehdi; Boitiaux, J.F.; Tadié, Jean‐Marc; Cazes, Aurélie; Riquet, Marc; Naline, Emmanuel; Israël‐Biet, Dominique; Delclaux, Christophe

doi:10.1016/j.pupt.2010.12.004

Cited by 2 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased arginase activity has also been associated with airway hyperresponsiveness [33,34]; we previously demonstrated that increased arginase activity is involved in airway sensitivity in smokers [35]. Overall, elevated arginase activity may be one of the mechanisms underlying both pulmonary arterial dysfunction and bronchial dysfunction [36]. Studies with L-arg supplementation have shown inconsistent effects on both systemic and pulmonary endothelial functions [37][38][39].…”

Section: Discussionmentioning

confidence: 98%

Is arginase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?

Henno

Maurey

Pimpec‐Barthes

et al. 2015

4.3 Pulmonary Circulation and Pulmonary Vascular Disease

Self Cite

View full text Add to dashboard Cite

Background: Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The bioavailability of the potent vasodilator nitric oxide (NO) depends on competition between NO synthase-3 (NOS3) and arginases for their common substrate (L-arginine). We tested the hypothesis whereby tobacco smoking impairs pulmonary endothelial function via upregulation of the arginase pathway.

show abstract

Section: Discussionmentioning

confidence: 98%

Is arginase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?

Henno

Maurey

Pimpec‐Barthes

et al. 2015

4.3 Pulmonary Circulation and Pulmonary Vascular Disease

Self Cite

View full text Add to dashboard Cite

show abstract

“…Increased arginase activity has also been associated with airway hyperresponsiveness [ 33 , 34 ]; we previously demonstrated that increased arginase activity is involved in airway sensitivity in smokers [ 35 ]. Overall, elevated arginase activity may be one of the mechanisms underlying both pulmonary arterial dysfunction and bronchial dysfunction [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Is arginase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?

et al. 2015

Self Cite

View full text Add to dashboard Cite

BackgroundTobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The bioavailability of the potent vasodilator nitric oxide (NO) depends on competition between NO synthase-3 (NOS3) and arginases for their common substrate (L-arginine). We tested the hypothesis whereby tobacco smoking impairs pulmonary endothelial function via upregulation of the arginase pathway.MethodsEndothelium-dependent vasodilation in response to acetylcholine (Ach) was compared ex vivo for pulmonary vascular rings from 29 smokers and 10 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of L-arginine supplementation, arginase inhibition (by N(omega)-hydroxy-nor-l-arginine, NorNOHA) and NOS3 induction (by genistein) on vasodilation. Protein levels of NOS3 and arginases I and II in the pulmonary arteries were quantified by Western blotting.ResultsOverall, vasodilation was impaired in smokers (relative to controls; p < 0.01). Eleven of the 29 smokers (the ED+ subgroup) displayed endothelial dysfunction (defined as the absence of a relaxant response to Ach), whereas 18 (the ED− subgroup) had normal vasodilation. The mean responses to 10−4 M Ach were −23 ± 10% and 31 ± 4% in the ED+ and ED− subgroups, respectively (p < 0.01). Supplementation with L- arginine improved endothelial function in the ED+ subgroup (−4 ± 10% vs. -32 ± 10% in the presence and absence of L- arginine, respectively; p = 0.006), as did arginase inhibition (18 ± 9% vs. -1 ± 9%, respectively; p = 0.0002). Arginase I protein was overexpressed in ED+ samples, whereas ED+ and ED− samples did not differ significantly in terms of NOS3 expression. Treatment with genistein did not significantly improve endothelial function in ED+ samples.ConclusionOverexpression and elevated activity of arginase I are involved in tobacco-induced pulmonary endothelial dysfunction.

show abstract

Association of ex vivo vascular and bronchial dysfunctions in smokers

Cited by 2 publications

References 23 publications

Is arginase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?

Is arginase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?

Is arginase a potential drug target in tobacco-induced pulmonary endothelial dysfunction?

Contact Info

Product

Resources

About