Kohan D E, Padilla E
Department of Internal Medicine, Veterans Administration Medical Center, Salt Lake City, Utah 84132.
J Clin Invest. 1993 Mar;91(3):1235-40. doi: 10.1172/JCI116286.
Recent evidence has implicated endothelin-1 (ET-1) as an autocrine inhibitor of inner medullary collecting duct (IMCD) sodium and water transport. The regulators of IMCD ET-1 production are, however, largely unknown. Because of the unique hypertonic environment of the IMCD, the effect of varying extracellular tonicity on IMCD ET-1 production was evaluated. Increasing media osmolality from 300 to 450 mosmol with NaCl or mannitol but not urea caused a marked dose- and time-dependent reduction in ET-1 release by and ET-1 mRNA in cultured rat IMCD cells. In contrast, increasing osmolality had no effect on ET-1 production by rat endothelial or mesangial cells. To see if ET-1 varies in a similar manner in vivo, ET-1 production was assessed in volume expanded (lower medullary tonicity) or volume depleted (high medullary tonicity) rats. Urinary ET-1 excretion and inner medulla ET-1 mRNA were significantly reduced in volume depleted as compared to volume expanded animals. These results indicate that extracellular sodium concentration inhibits ET-1 production specifically in IMCD cells. We speculate that extracellular sodium concentration, via regulation of ET-1 production, provides a link between volume status and IMCD sodium and water reabsorption.
最近有证据表明，内皮素 -1（ET-1）作为髓质集合管（IMCD）钠和水转运的自分泌抑制剂。然而，IMCD中ET-1产生的调节因子在很大程度上尚不清楚。由于IMCD独特的高渗环境，评估了细胞外张力变化对IMCD中ET-1产生的影响。用NaCl或甘露醇而非尿素将培养基渗透压从300 mosmol提高到450 mosmol，导致培养的大鼠IMCD细胞中ET-1释放和ET-1 mRNA显著剂量和时间依赖性减少。相反，渗透压升高对大鼠内皮细胞或系膜细胞中ET-1的产生没有影响。为了观察ET-1在体内是否以类似方式变化，在容量扩张（髓质张力较低）或容量减少（髓质张力较高）的大鼠中评估了ET-1的产生。与容量扩张动物相比，容量减少的动物尿ET-1排泄和髓质内ET-1 mRNA显著降低。这些结果表明，细胞外钠浓度特异性抑制IMCD细胞中ET-1的产生。我们推测，细胞外钠浓度通过调节ET-1的产生，在容量状态与IMCD钠和水重吸收之间建立了联系。
