Choline potentiates the pressor response evoked by glycyl-glutamine or naloxone in haemorrhaged rats

Abstract

1. Severe blood loss initially lowers arterial pressure through a central mechanism that is thought to involve opioid and cholinergic neurons. The present study tested the hypothesis that simultaneous administration of a cholinergic agonist and an opioid receptor antagonist would produce a synergistic effect in the treatment of haemorrhage. Specifically, we tested whether choline, a precursor of acetylcholine, potentiates the pressor effect of the beta-endorphin derived peptide glycylglutamine (Gly-Gln) or the opioid receptor antagonist naloxone following acute haemorrhage. 2. Conscious rats were treated intracerebroventricularly (i.c.v.) with choline chloride ( 180 nmol) alone or combined with Gly-Gln ( 10 nmol) or naloxone ( 10 nmol) 2 min after blood withdrawal (2.5 mL/100 g bodyweight over 20 min) was completed; mean arterial pressure and heart rate were monitored for 30 min. 3. Combined treatment with choline and Gly-Gln elevated mean arterial pressure but did not affect heart rate significantly. Choline and Gly-Gln had no effect on cardiovascular function when administered alone to haemorrhaged rats or when given together to normotensive animals. Choline also potentiated the pressor and tachycardic effect of naloxone in haemorrhaged rats. 4. These data show that choline potentiates the pressor effect of Gly-Gln and naloxone in haemorrhaged rats.