Analysis of responses to 5-hydroxytryptamine (serotonin) in the hindlimb vascular bed of the cat

Responses to 5-HT, the 5-HT2 receptor agonist α-methyl-5-hydroxytryptamine maleate (α-Met 5-HT), and the 5-HT1 receptor agonist 5-carboxamidotryptamine maleate (5-CT) were investigated in the hindlimb vascular bed of the cat under constant flow conditions. 5-CT, a 5-HT1 selective agonist, has been shown to possess vasodilator activity in other vascular beds studied. Injections of 5-HT (0.3-30 μg), α-Met 5-HT (3-100 μg), and 5-CT (1-30 μg) into the hindlimb perfusion circuit caused dose-related increases in hindlimb perfusion pressure. Responses to 5-HT, α-Met 5-HT, and 5-CT were not altered by the cycloxgenase inhibitor, meclofenemate (2.5 mg/kg iv), or nonselective α-receptor blocking agent, phentolamine (1 mg/kg iv). Responses to 5-HT, α-Met 5-HT, and 5-CT were blocked by ketanserin (5 mg/kg iv), a 5-HT2 selective antagonist, in a dose that did not alter responses to norepinephrine, U46619 (thromboxane mimic), or angiotensin II. Moreover, responses to 5-HT, α-Met 5-HT and 5-CT were blocked by ketanserin and a vasodilator response was not unmasked. These data suggest that the responses to 5-HT, α-Met 5-HT and 5-CT are not dependent on the activation of α-receptors, thromboxane receptors, or angiotensin receptors but are modulated by 5-HT receptors in the hindlimb vascular bed of the cat. Furthermore, these data may be interpreted to suggest that 5-HT1 receptors do not play an active role in mediating responses to 5-HT in the hindlimb vascular bed of the cat.