An increase in endogenous central
histamine concentration after inhibition of
histamine N-methyltransferase (HNMT) activity reverses critical
hypotension and improves the survival of rats in haemorrhagic
shock. The purpose of the study was to examine the involvement of the sympathetic nervous system in this endogenous central
histamine-induced
resuscitation. Experiments were carried out in ethylurethane-anaesthetised male Wistar rats subjected to haemorrhagic
hypotension (mean arterial pressure MAP 20-25 mmHg), which led to the death of all control animals within 30 min. The HNMT inhibitor
metoprine (20 micro g; i.c.v.) administered 5 min after establishing the critical
hypotension increased the endogenous
histamine concentration, measured 20 min
after treatment, in the hypothalamus (534.33+/-67.52 vs. 423.98+/-54.17 ng/g wet tissue; P<0.05) and medulla oblongata (53.12+/-9.78 vs. 39.58+/-11.16 ng/g wet tissue; P<0.05). These responses were accompanied by plasma levels of
noradrenaline and
adrenaline 2.7 and 1.7 times higher respectively than in the control group ( P<0.01).
Metoprine evoked dose-dependent (5, 10, 20 micro g; i.c.v.) rises in MAP and heart rate (HR) that were significantly higher than those in normotensive animals, and resulted in a 100% survival rate at 2 h
after treatment (20 micro g; i.c.v.). The resuscitative effect was associated with rises in renal, hindquarters and mesenteric blood flows. The nicotinic
cholinoceptor antagonist
hexamethonium (3 mg/kg; i.v.) attenuated the MAP and HR changes, whereas the
muscarinic cholinoceptor blocker
methylatropine (2 mg/kg; i.v.) attenuated only the pressor effect.
Metoprine-induced MAP and regional haemodynamic effects were also reduced by alpha(1)- and alpha(2)-adrenoceptor antagonists
prazosin (0.5 mg/kg; i.v.) and
yohimbine (1 mg/kg; i.v.), while the beta-
adrenoceptor blocker
propranolol (1 mg/kg; i.v.) diminished only HR changes. Ganglionic transmission inhibitors and
adrenoceptor antagonists did not influence the survival rate at 2 h in the
metoprine-treated groups. Bilateral adrenal demedullation diminished the pressor effect of
metoprine, however, without influence on HR and survival at 2 h
after treatment. In conclusion, the study demonstrates the activation of the sympathetic nervous system elicited by endogenous central
histamine in haemorrhage-shocked rats and confirms its involvement in
histamine-induced
resuscitation.