Wagner, Carsten A. Loffing-Cueni, Dominique Yan, Qingshang Schulz, Nicole Fakitsas, Panagiotis Carrel, Monique Wang, Tong Verrey, François Geibel, John P. Giebisch, Gerhard Hebert, Steven C. Loffing, Johannes 2008-04-02 ROMK-deficient (<i>Romk</i>^–/–) mice exhibit polyuria, natriuresis, and kaliuresis similar to individuals with type II Bartter's form of hyperprostaglandin E syndrome (HPS; antenatal Bartter's syndrome). In the present study, we utilized both metabolic and clearance studies to define the contributions of specific distal nephron segments to the renal salt wasting in these mice. The effects of furosemide, hydrochlorothiazide, and benzamil on urinary Na⁺ and K⁺ excretion in both wild-type (<i>Romk</i>^+/+) and <i>Romk</i>^–/– mice were used to assess and compare salt transport by the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2)-expressing thick ascending limb (TAL), the Na⁺-Cl⁻ cotransporter (NCC)-expressing distal convoluted tubule (DCT1/DCT2), and the epithelial Na⁺ channel (ENaC)-expressing connecting segment (CNT) and collecting duct (CD), respectively. Whole kidney glomerular filtration rate was reduced by 47% in <i>Romk</i>^–/– mice. Furosemide-induced increments in the fractional excretion rate of Na⁺ and K⁺ and absolute excretion of Na⁺ and K⁺ were significantly blunted in <i>Romk</i>^–/– mice, consistent with a major salt transport defect in the TAL. In contrast, hydrochlorothiazide produced an exaggerated natriuresis in <i>Romk</i>^–/– mice, indicating upregulation of salt absorption by the DCT. Benzamil resulted in a similar increment in absolute Na excretion in both <i>Romk</i>^–/– and <i>Romk</i>^+/+, indicating no significant upregulation of Na⁺ transport by ENaC in ROMK null mice. Moreover, hydrochlorothiazide increased the fractional K⁺ excretion rate in <i>Romk</i>^–/– mice, confirming our recent observation that maxi-K channels contribute to distal K⁺ secretion in the absence of ROMK. application/pdf https://folia.unifr.ch/global/documents/300943 https://folia.unifr.ch/documents/300943/files/loffing_mmb.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00613.2007 info:eu-repo/semantics/openAccess License undefined American Journal of Physiology: Renal Physiology. - 2008, vol. 294, no. 6, p. F1373-F1380 ROMK knockout furosemide hydrochlorothiazide benzamil info:eu-repo/classification/udc/57 Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins http://purl.org/coar/resource_type/c_6501