Department of Nephrology, Second University of Naples, Naples, Italy.
J Nephrol. 2010 Nov-Dec;23 Suppl 16:S112-7.
Calcium homeostasis is altered in hypertensive patients. Indeed several investigators have reported that sodium-sensitive hypertension is associated with hypercalciuria. On the other hand, an independent clinical association exists between the occurrence of urolithiasis and hypertension, but the molecular mechanism(s) involved in stone formation by high blood pressure have not been so far clarified. To understand this association, it is obvious that we should analyze the effect of hypertension on the transport proteins involved in the renal calcium handling. In the kidney, the tubular reabsorption of calcium may proceed through transcellular and paracellular routes. At variance with the proximal tubule, along the distal segment, calcium transport is entirely sodium independent and occurs via the transcellular pathway. In particular, transcellular calcium reabsorption proceeds through a well-controlled sequence of events consisting of luminal calcium entry via the epithelial calcium channel (TRPV5), cytosolic diffusion of calcium bound to calbindin-D28K, and basolateral extrusion of calcium through the Na/Ca exchanger (NCX1) and plasma membrane Ca-ATPase (PMCA). It is highly likely that these proteins may be altered in hypertensive disease thus justifying and explaining the reported hypercalciuria. Experiments in hypertensive strains of animals exhibiting hypercalciuria may help to solve this puzzle.
钙稳态在高血压患者中发生改变。事实上，已有几位研究人员报告称，钠敏感型高血压与高钙尿症有关。另一方面，尿石症的发生与高血压之间存在独立的临床关联，但迄今为止尚未阐明高血压形成结石的分子机制。为了理解这种关联，我们显然应该分析高血压对参与肾脏钙处理的转运蛋白的影响。在肾脏中，钙的管状重吸收可能通过细胞内和细胞旁途径进行。与近端小管不同，沿着远端节段，钙转运完全不依赖于钠，并通过细胞内途径发生。具体而言，细胞内钙重吸收通过一系列受严格控制的事件进行，这些事件包括通过上皮钙通道 (TRPV5) 进入腔室的钙进入、与钙结合的钙结合蛋白 D28K 向细胞质扩散，以及通过 Na/Ca 交换器 (NCX1) 和质膜 Ca-ATP 酶 (PMCA) 将钙从基底外侧挤出。这些蛋白很可能在高血压疾病中发生改变，从而证明并解释了报告的高钙尿症。在表现出高钙尿症的高血压动物品系中的实验可能有助于解决这个难题。
