Receptor mediation of microvascular responses to serotonin in striated muscle

Abstract

Serotonin constricts large arterioles and dilates small arterioles in striated muscle. Our study aimed to identify the receptors that mediate this differential response. Rats were anesthetized with pentobarbital sodium, and the cremaster muscle was prepared for videomicroscopy. Serotonin, applied topically, caused a constriction of large (A1) arterioles that was attenuated by cyproheptadine, methysergide, and LY 53857 but not by MDL 7222, phentolamine, propranolol, or diphenhydramine. The 5-hydroxytryptamine (5-HT)-induced constriction of A1 arterioles was mimicked by alpha-CH3-5-HT but not by 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) or 5-carboxamidotryptamine (5-CT). In addition, 5-HT caused a dilation of small (A3 or A4) arterioles that was blocked by cyproheptadine and methysergide but not by LY 53857, MDL 7222, phentolamine, or propranolol. Diphenhydramine caused a slight increase in the small arteriole mean effective concentration to serotonin but did not change the maximal response. The serotonin-induced dilation of small arterioles was mimicked by 5-CT but not by alpha-CH3-5-HT or 8-OH-DPAT. These data indicate that the 5-HT-induced constriction of large A1 arterioles is mediated via a 5-HT2 or 5-HT1C receptor, whereas 5-HT-induced dilation of smaller arterioles appears to be mediated by a 5-HT1-like receptor.