Abstract
The influence of tetrandrine on arterial pressure and heart rate of pentobarbitone-anaesthetized and conscious normotensive and hypertensive rats (SH rats, renal hypertensive rats, DOCA-salt hypertensive rats) was investigated. Tetrandrine administered intravenously (i.v.) to these animals caused an acute, long-lasting and dose-dependent decrease in mean arterial pressure. Heart rate was not significantly altered. In pithed rats, tetrandrine injected intraarterially 15 min previously impaired the increase in diastolic pressure induced by i.v. B-HT 920, a highly selective alpha 2-adrenoceptor-stimulating agent, in a dose-dependent manner. In a low dose, a parallel displacement to the right was observed, whereas for higher doses the shift was non-parallel. A high dose of tetrandrine shifted the pressor response curve of the alpha 1-adrenoceptor agonist, methoxamine, only slightly to the right and did not depress the maximal response. Tetrandrine also caused a moderate rightward shift of the vasopressor effect curve of vasopressin applied i.v. Tetrandrine displayed only minor affinities for specific binding sites in rat brain membranes for [3H]-prazosin (alpha 1-adrenoceptors) and for [3H]-clonidine (alpha 2-adrenoceptors). The results obtained suggest that the hypotensive effect of tetrandrine may be related to an impairment of vasoconstrictor tone mediated by vascular postsynaptic alpha 2-adrenoceptors.
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