Reversal of haemorrhagic shock in rats by tetrahydroaminoacridine

The cardiovascular effects of tetrahydroaminoacridine (tacrine; THA) were i nvestigated in haemorrhaged rats. Intracerebroventricular (i.c.v.) injectio n of THA (10, 25 and 50 mug) restored blood pressure in a dose- and time-de pendent manner. Atropine (10 mug, i.c.v.), a muscarinic receptor antagonist , attenuated the presser response to THA (25 mug, i.c.v.), while mecamylami ne (50 mug, i.c.v.), a nicotinic receptor antagonist, caused only a slight blockade in the presser effect of THA. Simultaneous pretreatment with atrop ine and mecamylamine almost abolished the blood pressure effect of i.c.v. T HA (25 mug). Haemorrhage increased plasma levels of adrenaline, noradrenali ne, vasopressin and plasma renin activity. THA (25 mug, i.c.v.) administrat ion caused additional increases in vasopressin and adrenaline levels but no t of renin activity and noradrenaline levels. The reversal of hypotension b y THA was greatly attenuated by administration of either prazosin, an al-ad renoceptor antagonist (0.5 mg/kg, i.v.) or by the vasopressin V-1 receptor antagonist [beta -mercapto-beta,beta -cyclopenta-methylenepropionyl(1), O-M e-Tyr(2)-Arg(8)]-vasopressin (10 mug/kg, i.v.). Pretreatment of rats with b oth prazosin and the vasopressin antagonist simultaneously completely inhib ited the presser response. Intravenous administration of THA (1, 1.5 and 3 mg/kg) also reversed hypotension in rats. Atropine (10 mug, i.c.v.) greatly attenuated the presser response to THA (1.5 mg/kg, i.v.), while mecamylami ne (50 mug, i.c.v.) failed to change the presser effect of THA. In anaesthe tised haemorrhaged rats, THA (1.5 mg/kg, i.v.) increased blood pressure and survival time of the animals. These results show that centrally and periph erally injected THA reverses haemorrhagic hypotension and increases surviva l time in rats. Activation of central muscarinic and nicotinic receptors is involved in the presser response to i.c.v. THA. The presser effect of i.v. THA is solely mediated by central muscarinic receptors. Moreover, the incr ease in plasma adrenaline and vasopressin levels appears to be involved in the presser effect of THA. Copyright (C) 2001 S. Karger AG, Basel.