title: NO and EDHF pathways in pulmonary arteries and veins are impaired in COPD patients.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong & TEDA International Cardiovascular Hospital, Medical College, Nankai University, Tianjin, China. yangqs@cuhk.edu.hk
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Norihisa
authors.initials: N
authors.lastname: Shigemura
authors.forename: Malcolm John
authors.initials: MJ
authors.lastname: Underwood
authors.forename: Michael
authors.initials: M
authors.lastname: Hsin
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Xue
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: He
authors.forename: Cheuk-Man
authors.initials: CM
authors.lastname: Yu
mesh_terms: D000368:Aged; D001685:Biological Factors / Q000378:metabolism; D015153:Blotting, Western; D018450:Disease Progression; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011651:Pulmonary Artery / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D011667:Pulmonary Veins / Q000473:pathology*; D012720:Severity of Illness Index; D014664:Vasodilation
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III