Head Geoffrey A, Burke Sandra L
Baker Heart Research Institute, Commercial Road Prahran, St. Kilda Road Central, Melbourne, Victoria, 8008, Australia.
Hypertension. 2004 Mar;43(3):636-42. doi: 10.1161/01.HYP.0000116301.02975.aa. Epub 2004 Jan 26.
We determined whether the sympathetic excitatory responses to environmental stressors and the sympathoinhibitory responses to rilmenidine are altered by renovascular hypertension. Rabbits were made hypertensive with a clip on the right renal artery, and a left renal nerve recording electrode was implanted. After 3 or 6 weeks, the animals were given air-jet stress and loud noise stress before and after intravenous rilmenidine. Three and 6 weeks after renal clipping, mean arterial pressure was 28% and 36% greater than preclip values. Air-jet stress elicited a marked increase in renal sympathetic nerve activity, mean arterial pressure, and heart rate. Renal sympathetic nerve activity responses were much greater in hypertensive rabbits, but the pressor responses were similar to those observed in normotensive animals. Acute administration of rilmenidine decreased blood pressure more in hypertensive animals but with a much lesser inhibition of sympathetic activity. Rilmenidine markedly reduced increased sympathetic activity during air-jet stress in 3-week clipped rabbits but to a lesser extent in the other groups. These studies show that while sympathetic responses to stress were markedly enhanced in renal clip hypertensive rabbits, they did not result in greater pressor responses, thus suggesting that vascular neuroeffector mechanisms were not altered. By contrast, the increased effects of rilmenidine suggest a much greater contribution to the hypertension by the sympathetic nervous system, but one that is caused by an enhanced "nonvascular" neuroeffector mechanism. As such, sympathoinhibitory agents such as rilmenidine are very suitable and very effective agents for the treatment of renovascular hypertension.
我们研究了肾血管性高血压是否会改变对环境应激源的交感兴奋反应以及对利美尼定的交感抑制反应。通过夹住右肾动脉使兔子患高血压，并植入左肾神经记录电极。3周或6周后，在静脉注射利美尼定前后对动物施加喷气应激和噪音应激。肾动脉夹闭3周和6周后，平均动脉压分别比夹闭前的值高28%和36%。喷气应激引起肾交感神经活动、平均动脉压和心率显著增加。高血压兔子的肾交感神经活动反应要大得多，但升压反应与正常血压动物观察到的相似。急性给予利美尼定在高血压动物中降低血压的幅度更大，但对交感神经活动的抑制作用要小得多。利美尼定在夹闭3周的兔子中显著降低了喷气应激期间增加的交感神经活动，但在其他组中程度较小。这些研究表明，虽然肾动脉夹闭高血压兔子对压力的交感反应明显增强，但并未导致更大的升压反应，因此表明血管神经效应机制未改变。相比之下，利美尼定作用的增强表明交感神经系统对高血压的贡献更大，但这是由增强的“非血管”神经效应机制引起的。因此，像利美尼定这样的交感抑制药物是治疗肾血管性高血压非常合适且非常有效的药物。
