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

100%

Jochem J.

Journal of Physiology and Pharmacology

2004

tom 55

nr 1,1

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 µg) administered intracerebroventricularly (icv) 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 (MC4) receptor antagonist HS014 (5 µg; icv) 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 MC4 receptors, participate in endogenous central histamine-induced resuscitating effect in rats.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Jochem J.

1 2004

Wyniki wyszukiwania

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