Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 280; no. 5; pp. 856 - L865
• Main Authors: Liu, Q, Sham, J. S. K, Shimoda, L. A, Sylvester, J. T
• Format: Journal Article
• Language: English
• Published: United States 01.05.2001
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Bronchial Arteries - drug effects; Bronchial Arteries - metabolism; Bronchial Arteries - physiopathology; Caffeine - pharmacology; Calcium - metabolism; Calcium - pharmacology; Cell Survival; Endothelin-1 - metabolism; Endothelin-1 - pharmacology; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Hypoxia - metabolism; Hypoxia - physiopathology; In Vitro Techniques; Lung - blood supply; Lung - metabolism; Lung - physiopathology; Male; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary Artery - physiopathology; Receptors, Endothelin - metabolism; Ryanodine - pharmacology; Swine; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.280.5.L856

Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224 To determine the role of endothelium in hypoxic pulmonary vasoconstriction (HPV), we measured vasomotor responses to hypoxia in isolated seventh-generation porcine pulmonary arteries < 300   µm in diameter with (E+) and without endothelium. In E+ pulmonary arteries, hypoxia decreased the vascular intraluminal diameter measured at a constant transmural pressure. These constrictions were complete in 30-40 min; maximum at P O 2 of 2 mmHg; half-maximal at P O 2 of 40 mmHg; blocked by exposure to Ca 2+ -free conditions, nifedipine, or ryanodine; and absent in E+ bronchial arteries of similar size. Hypoxic constrictions were unaltered by indomethacin, enhanced by indomethacin plus N G -nitro- L -arginine methyl ester, abolished by BQ-123 or endothelial denudation, and restored in endothelium-denuded pulmonary arteries pretreated with 10 10 M endothelin-1 (ET-1). Given previous demonstrations that hypoxia caused contractions in isolated pulmonary arterial myocytes and that ET-1 receptor antagonists inhibited HPV in intact animals, our results suggest that full in vivo expression of HPV requires basal release of ET-1 from the endothelium to facilitate mechanisms of hypoxic reactivity in pulmonary arterial smooth muscle. vascular smooth muscle; internal diameter; calcium; acetylcholine; U-46619; potassium chloride