Send to

Choose Destination
See comment in PubMed Commons below
Am J Physiol Renal Physiol. 2008 Jun;294(6):F1366-72. doi: 10.1152/ajprenal.00608.2007. Epub 2008 Apr 2.

Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity.

Author information

Dept. of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar St., New Haven, CT 06520-8026, USA.


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.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center