Xie He-Hui, Shen Fu-Ming, Zhang Xiao-Fei, Jiang Yuan-Ying, Su Ding-Feng
Department of Pharmacology, Second Military Medical University, 325 Guo He Road, Shanghai 200433, China.
Eur J Pharmacol. 2006 Aug 14;543(1-3):77-82. doi: 10.1016/j.ejphar.2006.05.034. Epub 2006 Jun 2.
Besides blood pressure, blood pressure variability and baroreflex sensitivity maybe important factors determining organ damage in hypertension. This study was designed to investigate the effects of various antihypertensive drugs on blood pressure and blood pressure variability reductions, baroreflex sensitivity, and target organ damage in spontaneously hypertensive rats (SHR). The dose is 20 mg/kg/day for atenolol, and 10 mg/kg/day for nifedipine, irbesartan and hydrochlorothiazide. We used relatively low doses of drugs to avoid a very remarkable normalization of blood pressure in the treatment, which would make it much difficult to distinguish the contribution of blood pressure variability and baroreflex sensitivity to organ protection from that of blood pressure. Drugs at the aforementioned doses were mixed into rat chow. SHR were treated for 4 months. Blood pressure was then continuously recorded for 24 h. After the determination of baroreflex sensitivity, rats were killed for organ-damage evaluation. It was found that long-term treatment with atenolol, nifedipine, irbesartan or hydrochlorothiazide all markedly reduced blood pressure variability, enhanced baroreflex sensitivity, and produced significant organ protection. Compared with blood pressure level, blood pressure variability and baroreflex sensitivity values showed a much closer or similar relationship with organ-damage parameters in every treatment group of rats. Multiple-regression analysis showed that the decrease in left ventricular hypertrophy, the decrease in aortic hypertrophy and the amelioration in renal lesion were all most closely correlated with the increase in baroreflex sensitivity and the decrease in systolic blood pressure variability. In conclusion, long-term treatment with atenolol, nifedipine, irbesartan or hydrochlorothiazide produced organ protection in SHR. Besides the blood pressure reduction, the decrease in blood pressure variability and the restoration of baroreflex sensitivity may contribute to this organ protection.
除血压外，血压变异性和压力反射敏感性可能是决定高血压患者器官损害的重要因素。本研究旨在探讨各种抗高血压药物对自发性高血压大鼠（SHR）血压、血压变异性降低、压力反射敏感性及靶器官损害的影响。阿替洛尔剂量为20mg/kg/天，硝苯地平、厄贝沙坦和氢氯噻嗪剂量为10mg/kg/天。我们使用相对低剂量的药物以避免治疗中血压非常显著地正常化，这会使区分血压变异性和压力反射敏感性对器官保护的作用与血压的作用变得更加困难。将上述剂量的药物混入大鼠食物中。对SHR治疗4个月。然后连续记录24小时血压。在测定压力反射敏感性后，处死大鼠进行器官损害评估。结果发现，长期使用阿替洛尔、硝苯地平、厄贝沙坦或氢氯噻嗪治疗均能显著降低血压变异性，增强压力反射敏感性，并产生显著的器官保护作用。与血压水平相比，各治疗组大鼠的血压变异性和压力反射敏感性值与器官损害参数的关系更为密切或相似。多元回归分析表明，左心室肥厚的减轻、主动脉肥厚的减轻和肾损害的改善均与压力反射敏感性的增加和收缩压变异性的降低最为密切相关。总之，长期使用阿替洛尔、硝苯地平、厄贝沙坦或氢氯噻嗪可对SHR产生器官保护作用。除降低血压外，血压变异性的降低和压力反射敏感性的恢复可能有助于这种器官保护。
