Kidney-specific genetic deletion of both AMPK α-subunits causes salt and water wasting.

Kidney-specific genetic deletion of both AMPK α-subunits causes salt and water wasting. Am J Physiol Renal Physiol. 2017 Feb 01;312(2):F352-F365 Authors: Lazo-Fernández Y, Baile G, Meade P, Torcal P, Martínez L, Ibañez C, Bernal ML, Viollet B, Giménez I Abstract AMP-activated kinase (AMPK) controls cell energy homeostasis by modulating ATP synthesis and expenditure. In vitro studies have suggested AMPK may also control key elements of renal epithelial electrolyte transport but in vivo physiological confirmation is still insufficient. We studied sodium renal handling and extracellular volume regulation in mice with genetic deletion of AMPK catalytic subunits. AMPKα1 knockout (KO) mice exhibit normal renal sodium handling and a moderate antidiuretic state. This is accompanied by higher urinary aldosterone excretion rates and reduced blood pressure. Plasma volume, however, was found to be increased compared with wild-type mice. Thus blood volume is preserved despite a significantly lower hematocrit. The lack of a defect in renal function in AMPKα1 KO mice could be explained by a compensatory upregulation in AMPK α2-subunit. Therefore, we used the Cre-loxP system to knock down AMPKα2 expression in renal epithelial cells. Combining this approach with the systemic deletion of AMPKα1 we achieved reduced renal AMPK activity, accompanied by a shift to a moderate water- and salt-wasting phenotype. Thus we confirm the physiologically ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research