Endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats--studies with histamine N-methyltransferase inhibitor SKF 91488.

Abstract

OBJECTIVE AND DESIGN:

Activation of the histaminergic system is associated with mobilisation of compensatory mechanisms in response to the action of stimuli which disturb homeostasis. Therefore, the effects of endogenous histamine in central cardiovascular regulation were studied in a rat model of irreversible haemorrhagic hypotension.

MATERIAL:

Cardiovascular parameters were measured in 66 and central histamine concentrations in 12 male Wistar rats anaesthetised with ketamine/xylazine.

TREATMENT:

Haemorrhage-shocked rats with mean arterial pressure (MAP) 20-25 mmHg were injected intracerebroventricularly (icv) with histamine N-methyltransferase inhibitor SKF 91488 after icv pre-treatment with H, H2 and H3 histamine receptor antagonists--chlorpheniramine (100 nmol), ranitidine (200 nmol) and thioperamide (100 nmol), respectively, or saline.

METHODS:

Arterial pressure and heart rate (HR) changes were monitored within 2 h after icv treatment, or to death if it occurred earlier. Histamine concentrations were measured using enzyme immunoassay. ANOVA followed by a test of Neuman-Keules, and Fisher's exact test were used to compare the results.

RESULTS:

SKF 91488 produced dose-dependent, significantly higher compared to normovolaemic animals, increases in MAP and HR with the improvement in survival rates. The action of SKF 91488 (100 microg) was associated with an increase in endogenous histamine concentrations in the cerebral cortex (1.19 +/- 0.09 vs. 0.77 +/- 0.21 nmol/g; p < 0.05), hypothalamus (5.62 +/- 0.68 vs. 4.18 +/- 0.45 nmol/g; p < 0.01) and medulla oblongata (0.53 +/- 0.17 vs. 0.29 +/- 0.05 nmol/g; p < 0.05) in comparison to saline-treated animals. SKF 91488-induced effects were inhibited by chlorpheniramine, whereas neither ranitidine nor thioperamide influenced the action.

CONCLUSION:

Endogenous central histamine, after SKF 91488 treatment, via activation of H, receptors produces reversal of hypotension, with improvement in the survival rate at 2 h after treatment, in rats subjected to critical haemorrhagic hypovolaemia.

• Authors: J Jochem
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 51 Issue 11 Pg. 551-6 (Nov 2002) ISSN: 1023-3830 [Print] Switzerland
• PMID: 12540019 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Histamine Antagonists
• SK&F 91488
• Histamine
• Histamine N-Methyltransferase
• Dimaprit

Topics

• Animals
• Blood Pressure (drug effects, physiology)
• Brain Chemistry (drug effects, physiology)
• Dimaprit (administration & dosage, analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Heart Rate (drug effects)
• Histamine (metabolism, physiology)
• Histamine Antagonists (pharmacology)
• Histamine N-Methyltransferase (antagonists & inhibitors)
• Hypotension (etiology, physiopathology)
• Injections, Intraventricular
• Male
• Rats
• Rats, Wistar
• Shock, Hemorrhagic (complications, physiopathology)
• Survival