5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo |
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Authors: | William F Jackson Armond Daci Janice M Thompson Gregory D Fink Stephanie W Watts |
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Institution: | 1. Department of Pharmacology & Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA;2. Department of Pharmacology & Toxicology, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA
Department of Pharmacy, Faculty of Medicine, University of Prishtina “Hasan Prishtina”, Prishtina, Kosovo |
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Abstract: | Objective Serotonin (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. Methods Cremaster 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. Results Topical 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. Conclusions 5-HT7 receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo. |
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Keywords: | 5-HT7 receptors arterioles serotonin skeletal muscle vascular smooth muscle vasodilation |
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