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


CONCLUSIONS
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.
Wang
Huai-Liang
HL
Department of Clinical Pharmacology, China Medical University, Shenyang 110001, China. hlwang@mail.cmu.edu.cn
Zhang
Xin-Hua
XH
Chang
Tian-Hui
TH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000037:antagonists & inhibitors; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors; D000470:Alkaloids / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D019332:Endothelin-1; D006168:Guinea Pigs; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000037:antagonists & inhibitors*
D000470:Alkaloids; D000959:Antihypertensive Agents; D044182:Benzylisoquinolines; D019332:Endothelin-1; D009478:Neuropeptide Y; D013189:SRS-A; D000804:Angiotensin II; C009438:tetrandrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid