THE MECHANISM OF THE HYPOTENSIVE EFFECT OF TETRANDRINE AND DEMETHYL-TETRANDRINE

Our previous studies indicated that tetrandrine and demethyl-tetrandrine caused a fall of blood pressure in anesthetized cats. Both compounds produced a direct as well as a reflex vasodilatation in the isolated rabbit's ear. In order to elucidate the mechanism of these effects, the interaction of these two alkaloids with acetylcholine and adrenaline, the influence on the sympathetic ganglian and the pressor response by occlusion of the common carotid arteries were investigated with the following results: (1) Tetrandrine 0.5 mg/kg and demethyl-tetrandrine 1.5 mg/kg injected intravenously prolonged the hypotensive effect of acetylcholine. The hypotensive effect of these two alkaloids was reduced to some extent by previous administration of atropine. (2) The effects of tetrandrine and demethyl-tetrandrine on blood pressure was not influenced by adrenaline and vice versa. (3) Tetrandrine and demethyl-tetrandrine did not reveal ganglion-blocking action, but during an abrupt and severe fall of blood pressure induced by these alkaloids, the sympathetic ganglion was temporarily excited (for about 5 min.) as indicated by spontaneous contraction and prolongation of contraction of the nictating membrane of the cat. (4) In view of the fact that these two alkaloids could inhibit or eliminate the pressor response to serial occlusion of the bilateral common carotid arteries in the cat, and that the hypotensive effect was not influenced by bilateral section of the sinus nerves, the vasomotor center or central sympathetic structures might be affected. (5) Repeated administration of demethyl-tetrandrine resulted in tachyphylaxis in its effect on blood pressure. (6) It can be concluded from the above experiments that the hypotensive effect of tetrandrine and demethyl-tetrandrine is caused by the following factors: (a) a direct and reflex vasodilatation, (b) an inhibition of vasomotor center or central sympathetic structures, and (c) a parasympathetic effect.