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.