Diverse vascular responses to serotonin in the conscious rabbit: effects of serotonin antagonists on renal artery spasm.

Vascular conductance in the mesenteric, hindquarter, and renal beds of the conscious rabbit was derived from regional blood flow (pulsed Doppler flowmeter) and ear artery pressure. After autonomic ganglion blockade (mecamylamine), serotonin (5-HT, 5-hydroxytryptamine) infusion, 3-60 micrograms/kg/min i.v., dilated the mesenteric and hindquarter beds but caused renal blood flow to fall to zero. Angiography confirmed that serotonin had caused the conduit renal arteries to spasm. This response was unaltered by 1 mg/kg prazosin but was antagonised by 0.5 mg/kg ketanserin and 0.5 mg/kg methysergide. Only the latter drug shifted the dilator-response curves in the other two beds. Methiothepin, 1 mg/kg, flattened both the dilator and constrictor response curves, perhaps by binding to an allosteric site on the serotonin receptor. 5-Carboxamidotryptamine (5-CT) caused about half the renal arteries to spasm at less than 30 ng/kg/min and dilated the other beds. From the antagonist data, we suggest that 5-HT2 receptors mediate the contraction of the renal artery, but that "5-HT1-like" receptors mediate the dilatation in the renal, mesenteric, and hindquarter beds in the conscious rabbit. 5-CT is not helpful in defining the receptors in the renal artery. The rather special spasmogenic response to serotonin in the renal artery is worthy of further research to reveal what factors may lead to large artery spasm.