Involvement of proopiomenalocortin-derived peptides in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats.

Abstract

An increase in endogenous central histamine concentrations, after loading with histamine precursor L-histidine or inhibition of histamine N-methyltransferase (HNMT) activity, produces the reversal of critical hypotension with improvement in survival of haemorrhage-shocked rats. In the present study, the involvement of proopiomelanocortin (POMC)-derived peptides in central histamine-induced resuscitating action was examined 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. HNMT inhibitor metoprine (20 microg) administered intracerebroventricularly (i.c.v.) at 5 min of critical hypotension produced a long-lasting pressor effect with a 100% survival rate at 2 h. The action was accompanied by 34.5% and 28.9% higher plasma concentrations of ACTH and alpha-MSH, respectively, in comparison to concentrations in the saline-injected group as measured 20 min after treatment. Melanocortin type 4 (MC(4)) receptor antagonist HS014 (5 microg; i.c.v.) inhibited metoprine-induced increase in mean arterial pressure, which resulted from decreased regional vascular resistance, however, it did not affect the heart rate and the survival at 2 h. On the other hand, glucocorticoid type II receptor blocker mifepristone (30 mg/kg; sc) had no effect. In conclusion, POMC-derived peptides, acting centrally via MC(4) receptors, participate in endogenous central histamine-induced resuscitating effect in rats.

• Authors: J Jochem
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 55 Issue 1 Pt 1 Pg. 57-71 (Mar 2004) ISSN: 0867-5910 [Print] Poland
• PMID: 15082867 (Publication Type: Comparative Study, Journal Article)

Chemical References

• HS014 cyclic peptide
• Peptides, Cyclic
• Receptor, Melanocortin, Type 4
• metoprine
• Mifepristone
• alpha-MSH
• Pro-Opiomelanocortin
• Histamine
• Adrenocorticotropic Hormone
• Pyrimethamine

Topics

• Adrenocorticotropic Hormone (blood)
• Animals
• Brain Chemistry (physiology)
• Disease Models, Animal
• Heart Rate (drug effects, physiology)
• Hemorrhage
• Hindlimb (blood supply, drug effects)
• Histamine (chemistry, metabolism, therapeutic use)
• Hypotension (physiopathology)
• Injections, Intraventricular
• Injections, Subcutaneous
• Male
• Mifepristone (administration & dosage, pharmacokinetics)
• Peptides, Cyclic (administration & dosage, pharmacokinetics)
• Pro-Opiomelanocortin (analogs & derivatives, chemistry, metabolism)
• Pyrimethamine (administration & dosage, analogs & derivatives, antagonists & inhibitors, pharmacokinetics)
• Rats
• Rats, Wistar
• Receptor, Melanocortin, Type 4 (administration & dosage, antagonists & inhibitors)
• Regional Blood Flow (drug effects)
• Renal Circulation (drug effects, physiology)
• Shock, Hemorrhagic (mortality, physiopathology, prevention & control)
• Splanchnic Circulation (drug effects)
• Time Factors
• alpha-MSH (blood)