biostudies-literatureVergara AInstituto de Salud Carlos IIIFONDO DE INVESTIGACIÓN SANITARIA-FEDER, ISCIIIBoehringer Ingelheim (Germany)Boehringer Ingelheim Pharma GmbH12823https://www.ebi.ac.uk/biostudies/studies/S-EPMC9656616biostudies-literatureUnknown23(21)Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliInternational journal of molecular sciencesEnhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.PMC9656616PI17/00257RICORS RD21/0005/0016Private fundingJacobs-Cacha CDominguez-Baez PVergara ASoler MJMartinez-Diaz IPieper MPLlorens-Cebria COrtiz AVan den Bosch MMBermejo SBenito BMartos NfalseEnhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagli2022-01-01T00:00:00Z2022 Oct2025-04-21T17:10:13.168Z2025-04-21T17:10:13.168ZS-EPMC96566163636161210.3390/ijms232112823