Effects of low-dose ketanserin on atherosclerosis in rats and rabbits.
Effects of low-dose ketanserin on atherosclerosis in rats and rabbits.
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DOI：
10.1139/y10-079
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发表时间：
2010-10
影响因子：
2.1
通讯作者：
Yong-sheng Yu;He-Hui Xie;Ling Li;Shu-wei Song;P. Han;G. Cai;D. Su
中科院分区：
文献类型：
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作者：
Yong-sheng Yu;He-Hui Xie;Ling Li;Shu-wei Song;P. Han;G. Cai;D. Su
本研究旨在验证小剂量酮色林可增强压力感受性反射活性，预防动脉粥样硬化早期病变的假设。实验一采用计算机血压监测系统，在清醒状态下测定了31只自发性高血压大鼠（SHR）的压力反射敏感性（BRS）。四周后，给大鼠服用维生素D3，并喂食高胆固醇饮食8周以诱导动脉粥样硬化。取心脏和盲肠作病理检查。SHR BRS与冠状动脉（r =-0.460，P < 0.01）和主动脉（r =-0.448，P < 0.05）呈负相关。在实验2中，SHR被分为3组（每组n = 10），并接受0.3、1.0和3.0 mg/kg剂量的酮色林（i.g.），分别在最小剂量（0.3 mg/kg）下，酮色林没有降低血压，但增强了BRS。在实验3中，SHR给予维生素D3，喂食高胆固醇饮食，同时用低剂量酮色林治疗。治疗组动脉粥样硬化评分明显低于对照组（冠脉评分：0.90 ± 0.14 vs.1.76 ± 0.27，P < 0.05;主动脉评分：1.00 ± 0.39 vs.2.18 ± 0.41，P < 0.05）。在实验4中，雄性新西兰白色家兔饲喂高胆固醇饲料，同时给予低剂量酮色林。治疗组动脉粥样硬化评分显著低于对照组（主动脉评分：0.26 ± 0.20 vs.0.60 ± 0.31，P < 0.05）。总之，本研究首次证明，低剂量酮色林在SHR和新西兰白色兔中至少部分通过增强动脉压力感受器反射功能来预防动脉粥样硬化的发展，而不依赖于其降压作用。
The present study was designed to test the hypothesis that a small dose of ketanserin, which enhances baroreflex activity, prevents the early lesions of atherosclerosis. In experiment 1, baroreflex sensitivity (BRS) was measured in 31 spontaneously hypertensive rats (SHRs) in a conscious state using a computerized blood pressure monitoring system. Four weeks later, the rats were administered vitamin D3 and fed a high-cholesterol diet for 8 weeks to induce atherosclerosis. Then their hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r = -0.460, P < 0.01) and aortic atherosclerosis (r = -0.448, P < 0.05) in SHR. In experiment 2, SHRs were divided into 3 groups (n = 10 in each group) and received a dose of ketanserin of 0.3, 1.0, and 3.0 mg/kg (i.g.), respectively. At the smallest dose (0.3 mg/kg), ketanserin did not lower blood pressure but enhanced BRS. In experiment 3, SHRs were administered vitamin D3, fed a high-cholesterol diet, and simultaneously treated with low-dose ketanserin. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (coronary score: 0.90 ± 0.14 vs. 1.76 ± 0.27, P < 0.05; aortic scores: 1.00 ± 0.39 vs. 2.18 ± 0.41, P < 0.05). In experiment 4, male New Zealand White rabbits were fed a high-cholesterol diet and treated with low-dose ketanserin at the same time. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (aortic scores: 0.26 ± 0.20 vs. 0.60 ± 0.31, P < 0.05). In conclusion, the present study demonstrated, for the first time, that low-dose ketanserin prevented the development of atherosclerosis independent of its blood pressure lowering action in SHRs and New Zealand White rabbits at least in part via enhancement of arterial baroreflex function.