Vasodilator and vasoconstrictor responses induced by 5-hydroxytryptamine in the in situ blood autoperfused hindquarters of the anaesthetized rat

In the present study we attempted to characterise the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT, serotonin) in in situ autoperfused rat hindquarters. Intra-arterial administration of the lowest doses of 5-HT used (0.12–12.5 ng/kg) induced vasodilator responses, whereas the highest doses (25–1000 ng/kg) produced vasoconstriction. The vasodilator effect was inhibited by methiothepin (a non-specific 5-HT1,2,5,6,7 receptor antagonist) and by a 5-HT1D/1B receptor antagonist, i.e., 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanolol (BRL 15572), but not by ritanserin (a selective 5-HT2 receptor antagonist), 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (SB 206553, a selective 5-HT2B/2C receptor antagonist) or mesulergine (a non-specific serotonergic antagonist that shows affinity to the 5-HT7 receptor). This vasodilator effect was mimicked by administration of a selective 5-HT1 receptor agonist – 5-carboxamidotryptamine (5-CT) – and by 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-1H-indol-3-yl]ethanamine (L-694,247, a selective 5-HT1D/1B receptor agonist). Methiothepin, but not mesulergine, inhibited 5-CT-induced vasodilatation and the selective 5-HT1D/1B receptor antagonist (BRL 15572) inhibited the vasodilator action induced by L-694,247.