Saruta T, Kanno Y, Hayashi K, Konishi K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kidney Int Suppl. 1996 Jun;55:S52-6.
This study defines the nature of the renal protective effects of calcium channel blockers (Ca blockers) and the effects of the Ca blocker, amlodipine, compared to those of the angiotensin-converting enzyme inhibitor (ACEI), enalapril, on the progression of renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHR) fed a high-salt diet. Furthermore, we studied the effects of various Ca blockers on the glomerular afferent and efferent arterioles using the isolated perfused hydronephrotic kidneys of six-week-old male Sprague-Dawley rats. In the first study, forty 6-week-old male SHRs which underwent 5/6 nephrectomy were equally divided into five groups. One group received no therapy. In two groups, therapy was started at four weeks post-nephrectomy, one with amlodipine and the other with enalapril. In the remaining two groups, amlodipine or enalapril therapy was started at eight weeks postnephrectomy. Amlodipine was more effective than enalapril in reducing proteinuria and glomerulosclerosis in the group that was started on drug therapy eight weeks after surgery. In the second study, at concentrations of 10(-6) to 10(-9) M, nifedipine, nicardipine and amlodipine dilated the afferent, but not the efferent, arteriole preconstricted with angiotensin II. On the other hand, efonidipine and manidipine clearly dilated angiotensin II-induced constriction of both the afferent and efferent arterioles. These results indicated that Ca blockers are effective at reducing renal injury in 5/6 nephrectomized SHR, and that they are more effective than ACEI in advanced stages of renal injury. The observation that only certain Ca blockers can dilate the efferent arteriole suggests that the renal protective effect of Ca blockers is not necessarily dependent on the dilation of the efferent arterioles.
本研究明确了钙通道阻滞剂（Ca阻滞剂）肾脏保护作用的本质，以及与血管紧张素转换酶抑制剂（ACEI）依那普利相比，Ca阻滞剂氨氯地平对高盐饮食喂养的5/6肾切除自发性高血压大鼠（SHR）肾损伤进展的影响。此外，我们使用6周龄雄性Sprague-Dawley大鼠的离体灌注积水肾，研究了各种Ca阻滞剂对肾小球入球小动脉和出球小动脉的影响。在第一项研究中，40只接受5/6肾切除的6周龄雄性SHR被平均分为五组。一组不接受治疗。两组在肾切除术后四周开始治疗，一组用氨氯地平，另一组用依那普利。其余两组在肾切除术后八周开始用氨氯地平或依那普利治疗。在术后八周开始药物治疗的组中，氨氯地平在降低蛋白尿和肾小球硬化方面比依那普利更有效。在第二项研究中，硝苯地平、尼卡地平和氨氯地平在浓度为10^(-6)至10^(-9) M时，可扩张被血管紧张素II预收缩的入球小动脉，但不能扩张出球小动脉。另一方面，依福地平马尼地平可明显扩张血管紧张素II诱导的入球小动脉和出球小动脉的收缩。这些结果表明，Ca阻滞剂对降低5/6肾切除SHR的肾损伤有效，且在肾损伤晚期比ACEI更有效。只有某些Ca阻滞剂能扩张出球小动脉这一观察结果表明，Ca阻滞剂的肾脏保护作用不一定依赖于出球小动脉的扩张。
