<i>m</i>-CPP, a 5-HT_2C Receptor Agonist That Modifies the Perfusion Pressure of the Hindquarter Vascular Bed of Anesthetized Rat

Abstract

In the present work we studied the actions of the intra-arterial administration of meta-chlorophenylpiperazine (m-CPP – a 5-HT_2C receptor agonist) in the hindquarters of the anesthetized rat. The lowest doses used (0.001, 0.01, 0.1, 0.25 and 0.5 µg/kg) induced vasodilatation whereas the highest doses produced vasoconstriction (1, 6.25, 12.5 and 25 µg/kg). Both vasodilatation and vasoconstriction were inhibited by the 5-HT_1,2receptor antagonist methiothepin, whereas the 5-HT₂receptorantagonist ritanserin blocked only the vasoconstrictor responses. 1-[4-(1-Adamantanecarboxamido)butyl]-4-(2-methoxyphenyl)piperazine (a 5-HT_1A receptor antagonist) and ICI 118,551 (a β₂-receptor antagonist) failed to modify the vasodilator responses of m-CPP. Both BRL 15572 (a 5-HT_1D receptor antagonist) and GR 55562 (a 5-HT_1B receptor antagonist) only partially inhibited this action. Our data reveal that m-CPP induces the 5-HT₁and/or non-specific vasodilator effect and 5-HT₂ vasoconstrictor effects in the hindquarter vascular bed of the rat.

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“…However, mCPP is far from being specific [113] and SDZ SER082 also blocks 5HT 2B receptors [114]; these considerations cast doubts on the real involvement of 5HT 2 receptors in the aforementioned effect also considering that no cardiovascular abnormality has been observed in 5HT 2C receptor ko mice [115]. Although 5HT 2C receptors have been traditionally considered as not present the cardiovascular system, a few studies suggested that 5HT 2C receptor activation could induce vasoconstriction in specific vascular beds such as the perfused hindquarter in anesthetized rats [116] or the mesenteric vascular bed [117]. While these results were obtained with agonists whose specificity could be questioned, Zhang et al [118] showed that in rats that developed pulmonary hypertension because of exposure to chronic hypoxia the expression of 5HT 2C receptors evaluated with Western blots, immunocytochemistry and RT-PCR did increase in smooth muscle cells of the pulmonary artery.…”