Involvement of the cholinergic system in the central histamine-induced reversal of critical haemorrhagic hypotension in rats

Abstract

Histamine, acting centrally as a neurotransmitter, evokes a reversal of haemorrhagic shock in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. In the present study, we demonstrate influences of cholinergic receptor antagonists on the central histamine-induced resuscitating action. Experiments were carried out in male anaesthetised Wistar rats subjected to a haemorrhagic hypotension of 20-25 mmHg, resulting in the death of all control animals within 30 min. Histamine (100 nmol) administered intracerebroventricularly (icv) at 5 min of critical hypotension produced a long-lasting pressor effect with increases in heart rate and peripheral blood flows, and a 100% survival at 2 h. Mean arterial pressure and blood flow changes were almost completely blocked by nicotinic receptor antagonist mecamylamine (246.3 nmol; icv) and partially inhibited by muscarinic receptor blocker atropine sulphate (14.8 nmol; icv). Cholinergic receptor antagonists given alone in the control saline-treated groups did not affect cardiovascular parameters in the post-bleeding period. In conclusion, there are interactions between the histaminergic and cholinergic systems, with an involvement of both nicotinic and muscarinic receptors, in the central cardiovascular regulation in haemorrhagic hypotension in rats.