The renal outer medullary potassium (ROMK) channel is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct and plays an important role in kidney physiology by regulating salt re-absorption. Loss-of-function mutations in the human ROMK channel are associated with antenatal type II Bartter’s syndrome, an autosomal recessive life-threatening salt-wasting disorder with mild hypokalemia. Although selective ROMK inhibitors would be expected to represent a new class of diuretic, this hypothesis had never been tested. A potent ROMK inhibitor caused concentration-dependent diuresis and natriuresis in normotensive rats and dogs. Unlike hydrochlorothiazide, the ROMK inhibitor did not cause significant urinary potassium loss or changes in plasma electrolyte levels. These data indicate that pharmacological inhibition of ROML has the potential for affording diuretic/natriuretic efficacy similar to that of clinically used diuretics but without dose limiting hypokalemia.
See article at J Pharmacol Exp Ther 2014, 348:153–164.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics