Hypotensive activity of tetrandrine in rats. Investigation into its mode of action.
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.
D000470:Alkaloids / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents; D001381:Azepines / Q000494:pharmacology; D044182:Benzylisoquinolines; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D000470:Alkaloids; D000959:Antihypertensive Agents; D001381:Azepines; D044182:Benzylisoquinolines; D011942:Receptors, Adrenergic, alpha; D014667:Vasopressins; C009438:tetrandrine; C024763:talipexole; D008729:Methoxamine; D003000:Clonidine; D011224:Prazosin