Department of Pharmacology, University of Buenos Aires, Buenos Aires, Argentina.
Hypertens Res. 2013 Apr;36(4):349-55. doi: 10.1038/hr.2012.209. Epub 2013 Jan 31.
An increase in blood pressure variability (BPV) contributes to the development of target organ damage associated with hypertension. Treatment with conventional β-blockers, such as atenolol, has been associated with an increase in BPV; however, the extrapolation of these results to third generation β-blockers with pleiotropic effects seems to be inappropriate. The cardiovascular effects of third generation β-blockers, carvedilol and nebivolol, were assessed in sinoaortic-denervated rats (SAD) and compared with the second generation β-blocker atenolol and the calcium channel blocker verapamil, with a special focus on short-term BPV. Male SAD rats were acutely treated with carvedilol, nebivolol, atenolol or verapamil at two different doses, and the effects on blood pressure and BPV were recorded. Short-term BPV was assessed by the s.d. of BP recordings. Beat-to-beat BPV was studied using spectral analysis to assess the vascular sympatholytic activity of carvedilol and nebivolol by estimating the effects of these drugs on the ratio of low frequency (LF) to high frequency (HF) BPV (LF/HF ratio). Nebivolol, carvedilol and the calcium channel blocker verapamil significantly attenuated short-term BPV at both doses in SAD animals, and there were no differences between the drugs. Conversely, atenolol did not modify baseline s.d. values at either dose. Carvedilol and nebivolol significantly reduced the LF/HF ratio in SAD rats compared with the effects of atenolol and verapamil, suggesting the ability of the third generation β-blockers to reduce vascular sympathetic activity. In conclusion, third generation β-blockers induce a marked reduction in short-term BPV in SAD rats compared to atenolol. Moreover, the ability of carvedilol and nebivolol to reduce short-term BPV in SAD rats is equivalent to that of verapamil, suggesting that these β-blockers may have an additional beneficial effect through their control of short-term variability to a similar extent to calcium channel blockers.
血压变异性（BPV）的增加导致与高血压相关的靶器官损伤的发展。传统的β受体阻滞剂（如阿替洛尔）的治疗与 BPV 的增加有关；然而，将这些结果推断到具有多效性的第三代β受体阻滞剂似乎并不合适。第三代β受体阻滞剂卡维地洛和比索洛尔的心血管作用在去窦神经大鼠（SAD）中进行了评估，并与第二代β受体阻滞剂阿替洛尔和钙通道阻滞剂维拉帕米进行了比较，特别关注短期 BPV。急性给予雄性 SAD 大鼠卡维地洛、比索洛尔、阿替洛尔或维拉帕米两种不同剂量，并记录血压和 BPV 的变化。短期 BPV 通过 BP 记录的标准差评估。使用频域分析研究逐搏 BPV，通过估计这些药物对低频（LF）与高频（HF）BPV 比值（LF/HF 比值）的影响，评估卡维地洛和比索洛尔的血管交感神经活性。比索洛尔、卡维地洛和钙通道阻滞剂维拉帕米在 SAD 动物中显著降低了两种剂量下的短期 BPV，且药物之间无差异。相反，阿替洛尔在两种剂量下均未改变基线 s.d.值。与阿替洛尔和维拉帕米相比，卡维地洛和比索洛尔显著降低了 SAD 大鼠的 LF/HF 比值，提示第三代β受体阻滞剂降低血管交感神经活性的能力。总之，与阿替洛尔相比，第三代β受体阻滞剂在 SAD 大鼠中引起短期 BPV 的显著降低。此外，卡维地洛和比索洛尔在 SAD 大鼠中降低短期 BPV 的能力与维拉帕米相当，这表明这些β受体阻滞剂可能通过控制短期变异性产生类似程度的额外有益作用，与钙通道阻滞剂相似。
