Involvement of arginine vasopressin in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats

Objective and design:Histamine is a potent stimulator of arginine vasopressin (AVP) release and therefore, the role of AVP was studied in the reversal of critical haemorrhagic hypotension induced by endogenous central histamine after inhibition of histamine N-methyltransferase (HNMT) activity in rats. Material:In 48 ethylurethane-anaesthetised male Wistar rats cardiovascular parameters and plasma hormone concentrations were measured. Treatment:Haemorrhage-shocked rats with mean arterial pressure (MAP) 20–25 mmHg were injected intracerebroventricularly (icv) with HNMT inhibitor metoprine (20 μg) after pre-treatment with V1a, V1b and V2 receptor antagonists – [β-mercapto-β,βcyclopentamethylenepropionyl1, O-me-Tyr2,Arg8]AVP (10 μg/kg; iv), SSR149415 (10 mg/kg; ip) and [adamantaneacetyl1,O-Et-D-Tyr2,Val4, aminobutyryl6,Arg8,9]AVP (10 μg/kg; iv), respectively, or saline. Methods:MAP, heart rate (HR) and regional haemodynamics were monitored within 2 h after treatment or to death if it occurred earlier. Plasma hormone concentrations were measured using enzyme immunoassays. ANOVA followed by Neuman-Keules test, and Fisher’s exact test were used to compare the results. Results:Metoprine produced a long-lasting increase in MAP, HR, renal, hindquarters and mesenteric blood flows, and a 100% survival at 2 h (P < 0.05 vs. the control group). The action was associated with increased plasma AVP concentration (587.5 ± 98.9 vs. 387.3 ± 125.2 pg/ml; P < 0.05) in comparison to the control group as measured at 20 min after treatment. V1a, but not V1b and V2, receptor antagonist inhibited metoprine-induced haemodynamic effects, with no influence on survival at 2 h. SSR149415 did not influence ACTH and adrenaline plasma concentrations in the metoprine-treated group. Conclusion:AVP, acting via V1a receptors, is involved in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats.