Mesenteric vasoconstrictor response to 5-hydroxytryptamine in the in situ blood autoperfused rat mesentery:: involvement of 5-HT2B and/or 5-HT2C receptor activation

Using a number of agonist and antagonist compounds, we attempted to characterize the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT) in the in situ blood perfused rat mesentery. An intra-arterial (i.a.) bolus injection of 5-HT increased mesenteric perfusion pressure in a dose-dependent way but did not change the systemic blood pressure. The selective 5-HT2 receptor agonists alpha-methyl-5-HT, 1-(3-chlorophenyl)piperazine dihydrochloride (m-CPP) and (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), caused a local vasoconstrictor effect in the autoperfused vascular mesenteric bed. Intra-arterial injection of 5-carboxamidotryptamine (5-CT) and 1-(m-chlorophenyl)-biguanide (m-CPBG) did not modify the mesenteric perfusion pressure. The vasoconstrictor effect elicited by 5-HT and alpha-methyl-5-HT was significantly decreased by ritanserin and by a selective 5-HT2B/2C receptor antagonist, N-3-pyridinyl-3,5-dihydro-5-methyl-benzo[1,2-b:4,5-b']dipyrrole-1(2H)-carboxamide hydrochloride (SB 206553), but was not modified by prazosin, propranolol. indomethacin or enalapril pretreatment. Our data suggest that the vasoconstrictor serotonergic response induced in the in situ autoperfused rat mesenteric vascular bed is mainly mediated by activation of 5-HT2B and/or 5-HT2C receptors. (C) 2000 Elsevier Science B.V. All rights reserved.