Effects of tetrandrine on smooth muscle contraction induced by mediators in pulmonary hypertension.
Abstract
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.
Keywords:
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.