Direct effect of cigarette smoke on human pulmonary artery tension |
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| Authors: | Jose Luis Ortiz Javier Milara Gustavo Juan Jose Luis Montesinos Manuel Mata Mercedes Ramón Esteban Morcillo Julio Cortijo |
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| Affiliation: | 1. Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain;2. Unidad de Investigación, Consorcio Hospital General Universitario, Valencia, Spain;3. Respiratory Unit, University General Hospital Consortium, Valencia, Spain;4. CIBERES, Health Institute Carlos III, Valencia, Spain;5. Clinical Pharmacology Unit, University Clinic Hospital, Valencia, Spain;1. Department of Internal Medicine, University of Alabama at Birmingham;2. Division of Pulmonary, Allergy, and Critical Care, Department of Medicine and University of Alabama at Birmingham Lung Health Center, University of Alabama at Birmingham;3. Birmingham Veterans Affairs Medical Center, Birmingham, AL;1. UGC Neumología, Hospital San Agustín, Avilés, Asturias, Spain;2. Fundación Respira, Sociedad Española de Neumología y Cirugía Torácica (SEPAR), Spain;3. Agencia de Salud Pública de Barcelona, Barcelona, Spain;4. Servicio de Neumología, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain;5. Servicio de Neumología, Hospital de Cabueñes, Gijón, Asturias, Spain;6. Programa Integrado de Investigación en Tuberculosis (PIITB) de SEPAR, Spain;1. Servicio de Oncología Radioterápica, Sección Radiofísica, Hospital Universitario Ramón y Cajal, crta. Colmenar Viejo km 7.1, 28034 Madrid, Spain;2. Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas, Serrano 113-bis, 28006 Madrid, Spain;3. Departamento de Física Atómica, Molecular y Nuclear, Universidad Complutense de Madrid, 28040 Madrid, Spain;1. Department of Hematology, University Hospital Virgen del Rocío/IBIS/CSIC/University of Seville, Seville, Spain;2. Department of Hematology, University Hospital of Salamanca, Salamanca, Spain;1. Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland |
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| 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. |
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