Effects of ketanserin on endotoxic shock and baroreflex function in rodents.
Effects of ketanserin on endotoxic shock and baroreflex function in rodents.
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DOI：
10.1093/infdis/jir609
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发表时间：
2011-11
期刊：
影响因子：
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通讯作者：
Chong Liu;Gu-fang Zhang;Shu-wei Song;G. Cai;Wen-hao Liu;C. Miao;D. Su
中科院分区：
文献类型：
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作者：
Chong Liu;Gu-fang Zhang;Shu-wei Song;G. Cai;Wen-hao Liu;C. Miao;D. Su
Ketanserin是一种5-羟色胺受体拮抗剂，临床应用于降压药，可增强血压反射功能。本研究验证了恢复压力反射功能是治疗脂多糖（LPS）引起的休克的有效方法。方法昆明小鼠腹腔注射LPS （30 mg/kg）诱导内源性休克。在LPS注射后立即给予酮色林（0.3、1、3或10 mg/kg；腹腔注射）。监测生存时间，分析LPS发作后血清细胞因子。酮色林对il -10缺陷小鼠和窦主动脉去神经小鼠的影响也进行了研究。最后，在Wistar-Kyoto （WKY）内毒素休克大鼠中检测酮色林对血压、心率和压力反射敏感性的影响。结果酮色林可显著延长内源性休克小鼠的生存时间，降低血清中肿瘤坏死因子α和白细胞介素1β水平。在10 mg/kg剂量下，酮色林也显著增加血清IL-10浓度。酮色林对il -10敲除小鼠的抗休克作用也很明显。然而，在窦主动脉失神经小鼠中，酮色林几乎没有抗休克作用。在WKY大鼠中，酮色林可明显预防LPS诱导的压力反射损伤，延长存活时间。结论酮色林可通过恢复压力反射功能改善内源性休克。
BACKGROUND Ketanserin, a 5-hydroxytryptamine receptor antagonist, is clinically used as an antihypertensive agent and could enhance baroreflex function. The present work tested the hypothesis that restoration of baroreflex function is an effective treatment for lipopolysaccharide (LPS)-induced shock. METHODS Kunming mice were injected with LPS (30 mg/kg; intraperitoneal) to induce endotoxic shock. Ketanserin (0.3, 1, 3, or 10 mg/kg; intraperitoneal) was administered immediately after LPS injection. Survival time was monitored, and serum cytokines were analyzed after the onset of LPS. Effects of ketanserin were also examined in IL-10-deficient mice and mice with sinoaortic denervation. Finally, effects of ketanserin on blood pressure, heart rate, and baroreflex sensitivity were examined in Wistar-Kyoto (WKY) rats with endotoxic shock. RESULTS Ketanserin significantly increased survival time and decreased serum levels of tumor necrosis factor α and interleukin (IL) 1β in mice with endotoxic shock. At a dose of 10 mg/kg, ketanserin also significantly increased serum IL-10 concentration. The antishock effect of ketanserin was also apparent in IL-10-knockout mice. In mice with sinoaortic denervation, however, ketanserin had little antishock effects. In WKY rats, ketanserin significantly prevented the baroreflex impairment induced by LPS and prolonged the survival time. CONCLUSIONS Ketanserin could ameliorate endotoxic shock by restoring baroreflex function.