Harris D C, Chan L, Schrier R W
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Am J Physiol. 1988 Feb;254(2 Pt 2):F267-76. doi: 10.1152/ajprenal.1988.254.2.F267.
To investigate the mechanisms whereby verapamil and dietary phosphate restriction slow progression of nephron loss after renal ablation, the effects of these maneuvers on inulin clearance (CIn), net sodium reabsorption (TNa+), oxygen consumption (QO2), and net glucose production (GP) were examined in isolated perfused normal and remnant kidneys. Preliminary studies characterized the isolated perfused remnant kidney perfusion. Adaptation to renal ablation was greater for QO2 (102% of normal), GP (138%), and kidney weight (79%) than CIn (51%) or TNa+ (40%). Verapamil (50 microM) lowered QO2 in remnant kidneys (1.64 +/- 0.24 vs. control 2.86 +/- 0.16 mumol.min-1.g-1, P less than 0.005), as did phosphate restriction (1.81 +/- 0.22 vs. control 3.05 +/- 0.40 mumol.min-1.g-1, P less than 0.05). These effects could not be accounted for by changes in CIn, TNa+, or GP and were not observed in normal kidneys. In summary 1) remnant kidneys are hypermetabolic compared with normal kidneys when assessed by QO2 and GP; 2) verapamil and phosphate restriction diminish the enhanced metabolic activity of remnant kidneys, an effect that is independent of TNa+; and thus 3) verapamil and phosphate restriction may slow progression of renal disease, at least in part by reducing renal metabolic demands.
为了研究维拉帕米和饮食中磷限制减缓肾切除术后肾单位丢失进展的机制，在分离灌注的正常和残余肾脏中检测了这些操作对菊粉清除率（CIn）、钠净重吸收（TNa +）、氧消耗（QO2）和葡萄糖净生成（GP）的影响。初步研究对分离灌注的残余肾脏灌注进行了表征。与CIn（51%）或TNa +（40%）相比，QO2（正常的102%）、GP（138%）和肾脏重量（79%）对肾切除的适应性更大。维拉帕米（50 microM）降低了残余肾脏的QO2（1.64±0.24对对照组2.86±0.16 μmol·min -1·g -1，P＜0.005），磷限制也有同样效果（1.81±0.22对对照组3.05±0.40 μmol·min -1·g -1，P＜0.05）。这些作用不能用CIn、TNa +或GP的变化来解释，在正常肾脏中未观察到。总之，1）通过QO2和GP评估时，残余肾脏与正常肾脏相比代谢亢进；2）维拉帕米和磷限制降低了残余肾脏增强的代谢活性，这种作用独立于TNa +；因此3）维拉帕米和磷限制可能至少部分通过降低肾脏代谢需求来减缓肾脏疾病的进展。
