Impaired Natriuretic Response to High-NaCl Diet plus Aldosterone Infusion in Mice Over-expressing Human CD39, an Ectonucleotidase (NTPDase1).

Impaired Natriuretic Response to High-NaCl Diet plus Aldosterone Infusion in Mice Over-expressing Human CD39, an Ectonucleotidase (NTPDase1). Am J Physiol Renal Physiol. 2015 Apr 15;:ajprenal.00125.2014 Authors: Zhang Y, Robson SC, Morris KL, Heiney KM, Dwyer KM, Kishore BK, Ecelbarger CM Abstract Extracellular nucleotides acting through P2 receptors facilitate natriuresis. To define how purinergic mechanisms are involved in sodium homeostasis, we used transgenic mice (TG) globally over-expressing human CD39 (hCD39, NTPDase1), an ectonucleotidase which hydrolyzes extracellular ATP/ADP to AMP, resulting in altered extracellular purine profile. On a high-sodium diet (HSD, 3.5% Na(+)), urine volume and serum sodium were elevated in TG mice without altering sodium excretion; however, there was significant impairment in HSD-induced decrease in urinary aldosterone in TG mice. Western analysis revealed significantly lower densities ((~)40%) for the β-subunit of the epithelial sodium channel (ENaC) in medulla, and the major band (85-kDa) of γ-ENaC in TG mice cortex. To evaluate aldosterone-independent differences, in a second experiment, aldosterone was clamped by osmotic minipump @ 20 µg/day and mice were fed HSD or a low-sodium diet (LSD, 0.03% Na(+)). Here, no differences in urine volume or osmolality, or serum aldosterone were found, but TG mice showed a modest, yet significant impairment in late natriuresis (days 3 and 4). Several ma...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research