Department of Pharmacology, Second Military Medical University, Shanghai 200433, PR China.
Can J Physiol Pharmacol. 2010 Nov;88(11):1054-60. doi: 10.1139/y10-079.
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.
本研究旨在验证小剂量酮色林增强压力反射活动可预防动脉粥样硬化早期病变的假说。在实验 1 中，使用计算机化血压监测系统在清醒状态下测量 31 只自发性高血压大鼠（SHR）的压力反射敏感性（BRS）。四周后，大鼠给予维生素 D3 并给予高胆固醇饮食 8 周以诱导动脉粥样硬化。然后取出心脏和主动脉进行病理检查。SHR 中 BRS 与冠状动脉（r = -0.460，P < 0.01）和主动脉粥样硬化（r = -0.448，P < 0.05）评分呈负相关。在实验 2 中，将 SHR 分为 3 组（每组 10 只），分别给予 0.3、1.0 和 3.0 mg/kg（ig）的酮色林剂量。在最小剂量（0.3 mg/kg）时，酮色林不降低血压，但增强 BRS。在实验 3 中，给予 SHR 维生素 D3、高胆固醇饮食，并同时给予低剂量酮色林治疗。治疗组的动脉粥样硬化评分明显低于对照组（冠状动脉评分：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，雄性新西兰白兔给予高胆固醇饮食，并同时给予低剂量酮色林治疗。治疗组的动脉粥样硬化评分明显低于对照组（主动脉评分：0.26 ± 0.20 vs. 0.60 ± 0.31，P < 0.05）。总之，本研究首次表明，小剂量酮色林可预防 SHR 和新西兰白兔的动脉粥样硬化发展，至少部分通过增强动脉压力反射功能，与降低血压作用无关。
