Renal function in NHE3-deficient mice with transgenic rescue of small intestinal absorptive defect
The degree to which loss of the NHE3 Na+/H+ exchanger in the kidney contributes to impaired Na+-fluid volume homeostasis in NHE3-deficient (Nhe3/) mice is unclear because of the coexisting intestinal absorptive defect. To more accurately assess the renal effects of NHE3 ablation, we developed a mous...
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Published in | American journal of physiology. Renal physiology Vol. 53; no. 6; pp. F1190 - F1198 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Physiological Society
01.06.2003
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Subjects | |
Online Access | Get full text |
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Summary: | The degree to which loss of the NHE3 Na+/H+ exchanger in the kidney contributes to impaired Na+-fluid volume homeostasis in NHE3-deficient (Nhe3/) mice is unclear because of the coexisting intestinal absorptive defect. To more accurately assess the renal effects of NHE3 ablation, we developed a mouse with transgenic expression of rat NHE3 in the intestine and crossed it with Nhe3/ mice. Transgenic Nhe3/ (tgNhe3/) mice tolerated dietary NaCl depletion better than nontransgenic knockouts and showed no evidence of renal salt wasting. Unlike nontransgenic Nhe3/ mice, tgNhe3/ mice tolerated a 5% NaCl diet. When fed a 5% NaCl diet, tgNhe3/ mice had lower serum aldosterone than tgNhe3/ mice on a 1% NaCl diet, indicating improved extracellular fluid volume status. Na+-loaded tgNhe3/ mice had sharply increased urinary Na+ excretion, reflective of increased absorption of Na+ in the small intestine; nevertheless, they remained hypotensive, and renal studies showed a reduction in glomerular filtration rate (GFR) similar to that observed in nontransgenic Nhe3/ mice. These data show that reduced GFR, rather than being secondary to systemic hypovolemia, is a major renal compensatory mechanism for the loss of NHE3 and indicate that loss of NHE3 in the kidney alters the set point for Na+-fluid volume homeostasis. |
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ISSN: | 1931-857X 1522-1466 |