Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
J Hypertens. 2011 May;29(5):945-52. doi: 10.1097/HJH.0b013e3283449529.
Treatment of renovascular hypertension with drugs that directly target the renin-angiotensin system may compromise glomerular filtration and renal excretory function, leading to renal failure. Centrally acting sympathoinhibitory agents also inhibit the renin-angiotensin system, so we determined whether this treatment modality alters renal excretory function in rabbits with renovascular hypertension.
Rabbits were equipped with bilateral renal artery flow probes and a renal nerve electrode. Hypertension was induced with a renal artery clip (2K1C) or rabbits were sham-clipped. After 2 weeks, a subcutaneous minipump was implanted to deliver rilmenidine (2.5 mg/kg per day) or vehicle for 3 weeks. Haemodynamic variables and renal function were studied under control conditions and during intravenous infusion of isotonic saline (154 mmol/l NaCl) at increasing rates of 4, 12 and 36 ml/kg per hour.
Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were greater in 2K1C rabbits than sham-clipped rabbits, but total urine flow, sodium excretion and glomerular filtration rate were similar in the two groups. In 2K1C rabbits, rilmenidine reduced MAP to close to control levels and reduced RSNA (40%), but did not significantly alter basal renal blood flow, glomerular filtration rate, urine flow or sodium excretion. The natriuretic response to isotonic saline load in 2K1C rabbits was not significantly altered by rilmenidine.
These observations show that chronic treatment of rabbits with renal artery stenosis with a centrally acting sympathoinhibitory agent, despite normalizing MAP, does not compromise renal excretory function. Thus, this treatment modality may be particularly useful in renovascular hypertension.
直接针对肾素-血管紧张素系统的药物治疗肾血管性高血压可能会损害肾小球滤过和肾脏排泄功能，导致肾衰竭。中枢作用的交感神经抑制药也抑制肾素-血管紧张素系统，因此我们确定这种治疗方式是否会改变肾血管性高血压兔的肾脏排泄功能。
兔子配备双侧肾动脉流量探头和肾神经电极。通过肾动脉夹（2K1C）或假夹诱导高血压。2 周后，植入皮下微量泵以每天 2.5mg/kg 的剂量输注利美尼定或载体 3 周。在对照条件下以及以 4、12 和 36ml/kg/小时的递增速率静脉输注等渗盐水（154mmol/l NaCl）时研究血流动力学变量和肾功能。
与假夹组相比，2K1C 兔的平均动脉压（MAP）和肾交感神经活动（RSNA）更高，但两组的总尿量、钠排泄量和肾小球滤过率相似。在 2K1C 兔中，利美尼定将 MAP 降低至接近对照水平并降低 RSNA（40%），但对基础肾血流量、肾小球滤过率、尿量或钠排泄没有显著影响。利美尼定对 2K1C 兔等渗盐水负荷的利尿反应没有明显改变。
这些观察结果表明，尽管中枢作用的交感神经抑制药可使肾动脉狭窄的兔子的 MAP 正常化，但对肾脏排泄功能没有损害。因此，这种治疗方式在肾血管性高血压中可能特别有用。
