title: Direct effect of cigarette smoke on human pulmonary artery tension.
abstract: 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 in vitro. 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ortiz
authors.forename: Javier
authors.initials: J
authors.lastname: Milara
authors.forename: Gustavo
authors.initials: G
authors.lastname: Juan
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Montesinos
authors.forename: Manuel
authors.initials: M
authors.lastname: Mata
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ramón
authors.forename: Esteban
authors.initials: E
authors.lastname: Morcillo
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology; D012906:Smoke; D014026:Nicotiana
chemical_list: C090663:N(6)-(1-iminoethyl)lysine; D012906:Smoke; D019335:Nitroarginine; D012701:Serotonin; D019001:Nitric Oxide Synthase; D008239:Lysine