Abstract: FR-PO577
Role of H,K-ATPase 2 in the Response to Mineralocorticoid Excess
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Morla, Luciana, CNRS EMR8228, Paris, France
- Lynch, I. Jeanette, University of Florida, Gainesville, Florida, United States
- Cheval, Lydie, CNRS EMR8228, Paris, France
- Lasaad, Samia, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Billiet, Justine, CNRS EMR8228, Paris, France
- Crambert, Gilles, CNRS EMR8228, Paris, France
- Wingo, Charles S., University of Florida, Gainesville, Florida, United States
Group or Team Name
- Physiologie Rénale et Tubulopathies.
Background
Aldosterone is a key hormone in blood pressure maintenance. In excess, aldosterone induces an increase in Na retention and blood volume. Natriuretic factors come into play to inhibit renal Na absorption and escape aldosterone effects. We have recently identified a Na secretion pathway (Morla et al 2016) involving the renal H,K-ATPase type 2 (HKA2) and the basolateral, bumetanide sensitive, cotransporter NKCC1, in the collecting duct. Here we ask if HKA2 plays a role in the aldosterone escape.
Methods
We treated wild type (WT) and HKA2KO (KO) mice with a normal salt diet (0.3% NaCl) and deoxycorticosterone pivalate (DOCP), an aldosterone analogue. We performed microperfusion of cortical collecting ducts (CCD) of DOCP treated WT and HKA2KO. We determined Na net fluxes before and after adding bumetanide to the bath. We studied mice in metabolic cages to determine daily Na urine excretion before and after DOCP treatment. During the escape phase: after 2 days of DOCP treatment (D2), we tested the effect of amiloride on urine Na excretion.
Results
DOCP treated WT and KO mice CCDs showed net Na reabsorption flux which declined over time in DOCP WT mice CCDs (p<0.04). This decrease was blunted in KO mice CCDs and in WT mice bumetanide-treated CCDs. DOCP induced urine Na retention in both mice groups 24h after DOCP injection. WT mice recovered a normal Na balance on D2 but KO mice excreted much more Na in their urines than WT mice and failed to keep a normal Na balance. Immunoblot analysis of D2 WT and KO mice kidneys showed similar increase of the expression of the NaCl cotransporter NCC. Interestingly, we found a smaller increase of the epithelal Na channel subunit αENaC (p<0.001) and a greater decrease of γENaC (p<0.05) in DOCP treated KO mice, when compared to DOCP treated WT mice suggesting ENaC could be less active in the KO mice. To confirm our hypothesis, we compared the effect of amiloride in WT and KO mice on D2 and found KO mice excreted less Na after amiloride treatment than WT mice (p<0.02).
Conclusion
Our data suggest that during the aldosterone escape, renal H,K-ATPase type 2 Na secretion in the CCD is necessary for Na balance maintenance. To compensate the exagerated Na retention, WT mice secrete Na through HKA2. In HKA2KO mice, ENaC inhibition in he CCD could allow to escape at the price of a greater Na loss.
Funding
- Government Support – Non-U.S.