OBJECTIVETo investigate the effects of propofol combined with indomethacin on the contractile function of isolated human pulmonary arteries.

METHODSHuman pulmonary artery preparations were obtained from patients undergoing surgery for lung carcinoma. The intrapulmonary arteries were dissected and cut into rings under microscope for treatment with propofol or propofol combined with indomethacin. In each group, the rings were divided into endothelium-intact and endothelium-denuded groups and mounted in a Multi Myograph system. In propofol group, the rings were preconstricted by U46619 to induce a sustained contraction, and propofol (10-300 mmol/L) was then applied cumulatively. In the combined treatment group, the rings were pretreated with indomethacin (100 µmol/L) for 30 min before application of U46619 to induce sustained contraction, and propofol (10-300 µmol/L) was added cumulatively after the tension became stable.

RESULTSPropofol (10-100 µmol/L) induced constrictions at low concentrations and caused relaxations at higher concentrations (100-300 µmol/L) in the pulmonary artery rings with prior U46619-induced contraction. Propofol caused stronger constrictions in endothelium-intact rings [EC=4.525∓0.37, Emax=(30.44∓2.92)%] than in endothelium-denuded rings [EC=4.699∓0.12, Emax=(31.19∓5.10)%, P<0.05]. Pretreatment of the rings with indomethacin abolished constrictions, and the relaxation was more obvious in endothelium-intact group [pD=3.713∓0.11, Emax=(98.72∓0.34)%] than in endothelium- denuded group [pD=3.54∓0.03, Emax=(94.56∓0.53)%, P<0.05].

CONCLUSIONPropofol induces constriction at low concentrations and relaxation at high concentrations in human intrapulmonary arteries with U46619-induced contraction. Indomethacin abolishes the constriction induced by propofol in isolated intrapulmonary arteries, suggesting that propofol potentiates U46619-mediated pulmonary vasoconstriction by promoting the concomitant production of prostaglandin by cyclooxygenase in pulmonary artery smooth muscle cells, and the mechanism for its relaxation effect may partly depend on the endothelium.