5‐HT₇ receptors mediate dilation of rat cremaster muscle arterioles in vivo

Abstract

ObjectiveSerotonin (5‐HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5‐HT7 receptors mediate arteriolar dilation to 5‐HT in skeletal muscle microcirculation.MethodsCremaster muscles of isoflurane‐anesthetized male Sprague‐Dawley rats were prepared for in vivo microscopy of third‐ and fourth‐order arterioles and superfused with physiological salt solution at 34°C. Quantitative real‐time PCR (RT‐PCR) was applied to pooled samples of first‐ to third‐order cremaster arterioles (2–4 rats/sample) to evaluate 5‐HT7 receptor expression.ResultsTopical 5‐HT (1–10 nmols) or the 5‐HT1/7 receptor agonist, 5‐carboxamidotryptamine (10–30 nM), dilated third‐ and fourth‐order arterioles, responses that were abolished by 1 μM SB269970, a selective 5‐HT7 receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5‐HT7 receptor knockout rats whereas arterioles in wild‐type litter mates dilated to 1 nmol 5‐HT, a response blocked by 1 μM SB269970. Quantitative RT‐PCR revealed that cremaster arterioles expressed mRNA for 5‐HT7 receptors.Conclusions5‐HT7 receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5‐HT‐induced hypotension, in vivo.