Tetrandrine, a Ca++ antagonist: effects and mechanisms of action in vascular smooth muscle cells.

Tetrandrine, an alkaloid extracted from the Chinese medicinal herb Radix stephania tetrandrae, has traditionally been used to treat hypertension. In the present study, the effect of tetrandrine on vascular smooth muscle was investigated by using the rat tail artery as a model of a resistance vessel. Tetrandrine relaxes the tension in tail artery helical strips produced by depolarization with 60 mM KCl. Further studies show that tetrandrine inhibits the KCl-induced intracellular Ca++ increase and L-type voltage-dependent Ca++ channel currents, suggesting that tetrandrine relaxes the vessel via inhibition of Ca++ influx through Ca++ channels. Tetrandrine also inhibits norepinephrine (NE)-induced vasocontraction in the presence of extracellular Ca++. It does not, however, inhibit NE-induced vasocontraction in the absence of extracellular Ca++. Tetrandrine also inhibits the NE-induced intracellular Ca++ increase in the presence of extracellular Ca++ and has no effect on the NE-induced intracellular Ca++ increase in the absence of extracellular Ca++. This suggests that tetrandrine also blocks NE-induced Ca++ influx but not NE-induced Ca++ release from the intracellular Ca++ stores. Furthermore, tetrandrine inhibits thapsigargin-induced intracellular Ca++ concentration increase, suggesting that, in addition to blocking Ca++ influx, tetrandrine also may interfere with the interaction between thapsigargin and Ca++ adenosine triphosphatase.