Direct effect of cigarette smoke on human pulmonary artery tension

Jose Luis Ortiz , Javier Milara , Gustavo Juan , Jose Luis Montesinos , Manuel Mata , Mercedes Ramón , Esteban J. Morcillo , Julio Cortijo

The effect of chronic cigarette smoke on pulmonary artery (PA) tension has been studied extensively; nevertheless, the direct effect of cigarette smoke is poorly understood. We investigated the direct effect of cigarette smoke extract (CSE) on PA tension in non-smokers, smokers, and COPD patients . PA samples from 35 patients who underwent lung resection were examined by measuring isometric tension in response to increasing serotonin concentrations. CSE dose-dependently inhibited the response to serotonin in smokers and COPD patients, and to a lesser extent in non-smokers. CSE-induced relaxation was similarly inhibited by the nonspecific nitric oxide synthase (NOS) inhibitor L-NOARG and the specific inducible NOS (iNOS) inhibitor L-NIL, mainly in non-smokers and smokers, and to a lesser extent in COPD patients. Immunostaining of iNOS in PA samples was greater for smokers and COPD patients compared with non-smokers, which explains the lesser effect of CSE on PA tension in non-smokers. Moreover, CSE induced the release of nitrite via iNOS in human PA smooth muscle cells. In conclusion, CSE inhibition of serotonin-induced PA contraction was mediated mainly by iNOS in non-smokers, smokers, and COPD patients, but in different ways, which may be explained by differential iNOS expression in the PA of these patients.

Mots clés: Cigarette smoke extract; Inducible nitric oxide synthase; Pulmonary artery; CSE; COPD; DMSO; eNOS; FEV1; FCS; FVC; HPAECs; HPASMCs; iNOS; NO; L-NOARG; L-NIL; PaCO; PaO; 5-HT; TLC

Jose Luis Ortiz, Javier Milara, Gustavo Juan, Jose Luis Montesinos, Manuel Mata, et al.. Direct effect of cigarette smoke on human pulmonary artery tension. Pulmonary Pharmacology & Therapeutics, 2010, 23 (3), pp.222. ⟨10.1016/j.pupt.2009.11.001⟩. ⟨hal-00628365⟩