Leong Patrick K K, Yang Li E, Lin Harrison W, Holstein-Rathlou Niels H, McDonough Alicia A
Dept. of Physiology and Biophysics, Univ. of Southern California Keck School of Medicine, 1333 San Pablo St., Los Angeles, CA 90089-9142, USA.
Am J Physiol Regul Integr Comp Physiol. 2004 Oct;287(4):R878-85. doi: 10.1152/ajpregu.00180.2004. Epub 2004 Jun 17.
Renal parathyroid hormone (PTH) action is often studied at high doses (100 microg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na(+) transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 +/- 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 microg.kg(-1).h(-1)) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na(+) reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli.
肾甲状旁腺激素(PTH)的作用通常是在高剂量(100微克PTH/千克)下进行研究的,这种剂量会显著降低平均动脉压,尽管是短暂的,这使得研究结果的解释变得复杂。关于急性低血压对近端小管钠(Na⁺)转运体的影响知之甚少。本研究旨在确定由主动脉夹闭或高剂量PTH(100微克PTH/千克)诱导的急性低血压对肾血流动力学以及近端小管钠/氢交换体3(NHE3)和IIa型钠-磷酸共转运蛋白(NaPi2)分布的影响。通过在山梨醇密度梯度上分级分离肾皮质膜来分析亚细胞分布。主动脉夹闭诱导的急性低血压(从100±3 mmHg降至78±2 mmHg)使尿量减少62%,近端小管的体积流量显著降低,表现为内源性锂清除率降低66%。然而,肾小球滤过率(GFR)以及NHE3和NaPi2的亚细胞分布没有显著变化。相比之下,高剂量PTH迅速(<2分钟)将动脉血压降至51±3 mmHg,减少尿量,并使NHE3和NaPi2从富含顶端标志物的低密度膜中移出。更低剂量(<1.4微克·千克⁻¹·小时⁻¹)的PTH不会改变血压,且具有利尿作用。总之,急性低血压本身会增加近端小管钠(Na⁺)重吸收,而不改变NHE3或NaPi2的亚细胞分布,这表明转运体向表面的转运不太可能是其机制;相比之下,高剂量PTH引起的低血压会阻断PTH的主要利尿作用,但不会抑制PTH刺激的NHE3和NaPi2向微绒毛基部的重新分布。