Am. J. Respir. Crit. Care Med., Volume 164, Number 4, August 2001, 709-713

Reduced Expression of Endothelial Nitric Oxide Synthase in Pulmonary Arteries of Smokers

JOAN A. BARBERÀ, VICTOR I. PEINADO, SALUD SANTOS, JOSEP RAMIREZ, JOSEP ROCA, and ROBERT RODRIGUEZ-ROISIN

Departments of Pulmonary Medicine and Pathology, Institut d'Investigacións Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain

Cigarette smoking has been associated with alterations in the structure and endothelial function of pulmonary arteries. Nitric oxide (NO) and endothelin-1 are endothelium-derived mediators with opposite effects on vascular tone and cell growth. To investigate whether cigarette smoking could induce changes in the synthesis of these mediators in pulmonary arteries, we compared the expression of both endothelial NO synthase (eNOS) and endothelin-1 in the lungs of smokers with that in nonsmokers. Lung tissue samples of 23 smokers and nine nonsmokers were studied. Expression of eNOS and endothelin-1 in pulmonary artery endothelium was evaluated by immunohistochemistry. In protein extracts of lung tissue, the content of eNOS protein was assessed by Western blot analysis and that of endothelin-1 by radioimmunoassay. The immunohistochemical expression of eNOS in arterial endothelium and the eNOS protein content in lung tissue were lower in the smokers than in the nonsmokers. No differences were shown in cell expression and protein content of endothelin-1 between both groups. We conclude that cigarette smoking is associated with reduced expression of eNOS in pulmonary arteries. The diminished synthesis of nitric oxide may contribute to the alterations in the structure and endothelial function of pulmonary vessels in cigarette-smoke-induced respiratory disease.

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