Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins

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

doi:10.1152/ajprenal.00613.2007

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Journal article

Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins

Wagner, Carsten A. Institute of Physiology, Center of Integrative Human Physiology, University of Zurich, Switzerland
Loffing-Cueni, Dominique Institute of Anatomy, University of Zurich, Switzerland - Department of Medicine, Unit of Anatomy, University of Fribourg, Switzerland
Yan, Qingshang Department of Cellular and Molecular Physiology, Yale Medical School, New Haven, USA
Schulz, Nicole Institute of Physiology, Center of Integrative Human Physiology, University of Zurich, Switzerland
Fakitsas, Panagiotis Institute of Physiology, Center of Integrative Human Physiology, University of Zurich, Switzerland
Carrel, Monique Institute of Anatomy, University of Zurich, Switzerland - Department of Medicine, Unit of Anatomy, University of Fribourg, Switzerland
Wang, Tong Department of Cellular and Molecular Physiology, Yale Medical School, New Haven, USA
Verrey, François Institute of Physiology, Center of Integrative Human Physiology, University of Zurich, Switzerland
Geibel, John P. Department of Cellular and Molecular Physiology, Yale Medical School, New Haven, USA - Department of Surgery, Yale Medical School, New Haven, USA
Giebisch, Gerhard Department of Cellular and Molecular Physiology, Yale Medical School, New Haven, USA
Hebert, Steven C. Department of Cellular and Molecular Physiology, Yale Medical School, New Haven, USA
Loffing, Johannes Institute of Anatomy, University of Zurich, Switzerland - Department of Medicine, Unit of Anatomy, University of Fribourg, Switzerland

02.04.2008

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American Journal of Physiology: Renal Physiology. - 2008, vol. 294, no. 6, p. F1373-F1380

English ROMK-deficient (Romk^–/–) 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 (Romk^+/+) and Romk^–/– 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 Romk^–/– mice. Furosemide-induced increments in the fractional excretion rate of Na⁺ and K⁺ and absolute excretion of Na⁺ and K⁺ were significantly blunted in Romk^–/– mice, consistent with a major salt transport defect in the TAL. In contrast, hydrochlorothiazide produced an exaggerated natriuresis in Romk^–/– mice, indicating upregulation of salt absorption by the DCT. Benzamil resulted in a similar increment in absolute Na excretion in both Romk^–/– and Romk^+/+, indicating no significant upregulation of Na⁺ transport by ENaC in ROMK null mice. Moreover, hydrochlorothiazide increased the fractional K⁺ excretion rate in Romk^–/– mice, confirming our recent observation that maxi-K channels contribute to distal K⁺ secretion in the absence of ROMK.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

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