NO and EDHF pathways in pulmonary arteries and veins are impaired in COPD patients

We investigated endothelial function of both pulmonary arteries and veins in patients with chronic obstructive pulmonary disease (COPD) of varying severity in regard to the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Lung tissues were obtained from patients undergoing lobectomy or pneumonectomy. Patients were grouped to control, moderate COPD, and severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Pulmonary arteries and veins were studied for endothelium-dependent relaxations. NO concentration was measured by electrochemical method. Protein expressions of eNOS and phosphorylated eNOS were determined by Western-blot. Endothelium-dependent relaxation was more significant in pulmonary arteries than in veins. The vasorelaxation was decreased in patients of moderate COPD and further decreased in severe COPD. The severity of endothelial dysfunction in both pulmonary arteries and veins correlated with the degree of airflow obstruction. COPD patients exhibited reduced endothelial NO production, decreased eNOS protein expression and decreased eNOS phosphorylation. The EDHF component was abolished in the pulmonary vasculature of patients with severe COPD. NO and EDHF pathways are both involved in the regulation of vascular tone in human pulmonary arteries and veins. Both pathways are impaired in COPD patients and the severity of the impairment increases with the progress of the disease. Downregulation of eNOS expression and inhibition of eNOS activation underlie the reduction of NO in COPD patients.