Effects of tetrandrine on smooth muscle contraction induced by mediators in pulmonary hypertension  

作　　者：WANG Huai-Liang, ZHANG Xin-Hua, CHANG Tian-HuiDepartment of Clinical Pharmacology, China Medical University, Shenyang 110001, China 

出　　处：《Acta Pharmacologica Sinica》2002年第12期1114-1120,共7页中国药理学报（英文版）

基　　金：Projects supported by National Natural Science Foundation of China.№ 39170846.

摘　　要：AIM: In attempt to characterize tetrandrine on pulmonary hypertension, biological activities induced by a range of mediators implicated in the pathogenesis of pulmonary hypertension were investigated. METHODS: Pulmonary artery rings and tracheal segments were contracted with couples of bioactive substances in which a series experiments including effects of tetrandrine on calcium agonist, endothelin, thromboxane A2, angiotensin II, neuropeptide Y, histamine, 5-methyl furmethide were performed, the influences of tetrandrine in the concentration of 1 to 30 micromol/L were investigated. RESULTS: Tetrandrine inhibited calcium agonist BayK8644, endothelin-1 and thromboxane A2 mimetic U46619, angiotensin II- and neuropeptide Y-induced contractile responses with depression of the maximal contraction of pulmonary artery rings in a varying extent. Tetrandrine inhibited leukotriene E4-induced concentration-response curve in a competitive antagonist manner with a pKB of (5.29+/-0.11) without any influence leukotriene C4, leukotriene D4, histamine, and 5-methyl furmethide induced contractile responses of guinea pig trachea. CONCLUSION: Tetrandrine may produce multiple pharmacological effects against calcium channel antagonist, U46619, endothelin-1,angiotension II, and neuropeptide Y induced vasoconstriction in rat pulmonary arteries in varying extent and inhibition of leukotriene E4 rather than C4, D4, histamine, and 5-methyl furmethide induced contractile responses on rat tracheal segments. These pharmacological characteristics are considered to contribute to its antihypertensive action during pulmonary hypertension.AIM:In attempt to characterize tetrandrine on pulmonary hypertension,biological activities induced by a range of mediators implicated in the pathogenesis of pulmonary hypertension were investigated.METHODS:Pulmonary artery rings and tracheal segments were contracted with couples of bioactive substances in which a series experiments including effects of tetrandrine on calcium agonist,endothelin,thromboxane A2,angiotensin II,neuropeptide Y,histamine,5-methyl furmethide were performed,the influences of tetrandrine in the concentration of 1 to 40μmol/L were investigated.RESULTS:Tetrandrine inhibited calcium agonist BayK8644,endothelin-1 and thromboxane A2 mimetic U46619,angiotensin II-and neuropeptide Y-induced contractile responses with depression of the maximal contraction of pulmonary artery rings in a varying extent.Tetrandrine inhibited leukotriene E4-induced concentration-response curve in a competitive antagonist manner with a pKB of (5.29±0.11) without any influence leukotriene C4,leukotriene D4,histamine,and 5-methylfurmethide induced contractile responses of guinea pig trachea.CONCLUSION:Tetrandrine may produce multiple pharmacological effects against calcium channel antagonist,U46619,endothelin-1,angiotension II,and neuropeptide Y induced vasoconstriction in rat pulmonary arteries in varying extent and inhibition of leukotriene E4 rather than C4,D4,histamine,and 5-methyl furmethide induced contractile responses on rat tracheal segments.These pharmacological characteristics are considered to contribute to its antihypertensive action during pulmonary hypertension.

关 键 词：15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid 3-Pyridinecarboxylic acid  1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-  Methylester Alkaloids Angiotensin II Animals Antihypertensive Agents BENZYLISOQUINOLINES Endothelin-1 Guinea Pigs Hypertension  Pulmonary Male Muscle Contraction Muscle  Smooth  Vascular Neuropeptide Y Pulmonary Artery RATS Rats  Sprague-Dawley Research Support  Non-U.S. Gov't SRS-A 

分 类 号：R544.1[医药卫生—心血管疾病]