5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo
5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo
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DOI：
10.1111/micc.12808
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发表时间：
2023-05-19
期刊：
影响因子：
2.4
通讯作者：
Watts，Stephanie W.
中科院分区：
文献类型：
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作者：
Jackson，William F.;Daci，Armond;Watts，Stephanie W.
目的体内血清素（5-HT）输注会导致低血压和总外周阻力下降。然而，介导这种反应的血管段和受体仍然存在疑问。我们假设5-HT7受体在骨骼肌微循环中介导小动脉扩张至5-HT。方法制备异氟烷麻醉的雄性Sprague-Dawley大鼠的提肌，用于体内三级和四级小动脉显微镜检查，并在34℃下灌注生理盐溶液。将定量实时 PCR (RT-PCR) 应用于一级至三级提睾小动脉的合并样本（2-4 只大鼠/样本），以评估 5-HT7 受体表达。结果局部 5-HT (1-10nmol) 或 5-HT1/7 受体激动剂 5-羧酰胺色胺 (10-30nM)、扩张的第三级和四级小动脉的反应被 1μM SB269970（一种选择性 5-HT7 受体拮抗剂）消除。相反，SB269970 不会抑制由毒蕈碱激动剂醋甲胆碱（100nmol）诱导的扩张。 5-羟色胺（10nmol）无法扩张 5-HT7 受体敲除大鼠的提睾小动脉，而野生型同窝大鼠的小动脉扩张至 1nmol 5-HT，这一反应被 1μM SB269970 阻断。定量 RT-PCR 显示提睾小动脉表达 5-HT7 受体的 mRNA。结论 5-HT7 受体介导骨骼肌中小动脉的扩张，并可能导致体内 5-HT 诱导的低血压。
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‐HT7receptors 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‐HT7receptor expression.ResultsTopical 5‐HT (1–10 nmols) or the 5‐HT1/7receptor agonist, 5‐carboxamidotryptamine (10–30 nM), dilated third‐ and fourth‐order arterioles, responses that were abolished by 1 μM SB269970, a selective 5‐HT7receptor 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‐HT7receptor 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‐HT7receptors.Conclusions5‐HT7receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5‐HT‐induced hypotension, in vivo.