Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rat
Paulo de Coelho Castro, Thiago M. Santos-Rios, Flavia L. Martins, Renato O. Crajoinas, Marcos V. Caetano, Lucília M. A. Lessa, Weverton Machado Luchi, James A. McCormick, Adriana C. C. Girardi
Abstract
This study suggests that reduced NHE3-mediated sodium reabsorption in the renal proximal tubule may account, at least in part, for the BP-lowering effect of SGLT2 inhibitors in the setting of hypertension. It also demonstrates that chronic treatment with SGLT2 inhibitors upregulates NCC activity, phosphorylation, and expression in the distal tubule of normotensive but not hypertensive rats. SGLT2 inhibitor-mediated upregulation of NCC seems crucial to counteract proximal tubule natriuresis in subjects with normal BP.
Topics & Concepts
EmpagliflozinDownregulation and upregulationEMPAEndocrinologyInternal medicineMedicineChemistryDiabetes mellitusPharmacologyType 2 diabetesBiochemistryMineralogyElectron microprobeGeneDiabetes Treatment and ManagementParathyroid Disorders and TreatmentsIon Transport and Channel Regulation