Superoxide and endothelium‐dependent constriction to flow in porcine small pulmonary arteries

• Published in: British journal of pharmacology Vol. 124; no. 2; pp. 331 - 336
• Main Authors: Liu, Qiang, Wiener, Charles M, Flavahan, Nicholas A
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.1998; Nature Publishing
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Acetylcholine - pharmacology; Animals; Aorta, Thoracic; Biological and medical sciences; Blood vessels and receptors; Cell physiology; Dose-Response Relationship, Drug; EDCF; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; endothelium‐derived constricting factor; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Male; microcirculation; Molecular and cellular biology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Pulmonary Circulation - drug effects; Pulmonary Circulation - physiology; Responses to growth factors, tumor promotors, other factors; Shear stress; Superoxide Dismutase - pharmacology; Swine; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vertebrates: cardiovascular system; Lung; Superoxide dismutase; Respiratory system; Endothelium derived nitric oxide factor; Vasodilation; Microcirculation; Vasomotricity; Vascular resistance; Blood vessel; Ungulata; Endothelium derived contracting factor; Enzyme; Vasoconstriction; Enzyme inhibitor; Pulmonary artery; Nitric-oxide synthase; Endothelium; Pig; Vertebrata; Mammalia; Shear stress; Acetylcholine; Artiodactyla; Oxidoreductases; Circulatory system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701846

The aim of this study was to determine the response of porcine small pulmonary arteries to intralumenal flow and to identify the cellular mechanisms and potential mediators involved in the response. Porcine small pulmonary arteries were isolated from a branch of the main intrapulmonary artery of the lower lung lobe and studied in a perfusion myograph system that allowed independent control of transmural pressure and intralumenal flow. At a transmural pressure of 20 mmHg, the baseline internal diameter (BID) of the arteries was 251.2±16.1 μm (n=16). Under quiescent conditions or during constriction with U46619 to ∼60% of BID, intralumenal flow caused reversible constriction in arteries with endothelium (in the presence of U46619, flow decreased diameter from 60.0±2.5% to 49.5±3.0% BID at 10 μl min−1, n=16, P<0.05) but no change in diameter of arteries without endothelium. In the presence of superoxide dismutase (SOD, 150 u ml−1), the response to flow was converted from constriction to vasodilatation (in presence of U46619 and SOD, flow increased diameter from 54.2±3.4% to 76.7±4.5% BID at 10 μl min−1, n=10, P<0.05). Inhibition of NO synthase with L‐NAME (3×10−5 M) abolished the flow‐induced vasodilatation occurring in the presence of SOD and the flow‐induced constriction occurring in the absence of SOD. In arteries with endothelium, L‐NAME (3×10−5 M) caused significant vasoconstriction, whereas SOD did not alter vasomotor tone. Acetylcholine (10−8 to 10−6 M) caused endothelium‐dependent relaxation of small pulmonary arteries that was not significantly affected by SOD (150 u ml−1) but was inhibited by L‐NAME (3×10−5 M). These results suggest that in small, porcine, isolated pulmonary arteries, intralumenal flow increases the production of NO but this is obscured by the generation of superoxide which causes vasoconstriction.