OS 05-04 EMPAGLIFLOZIN EXERTS CARDIO- AND NEPHRO-PROTECTIVE EFFECTS IN COHEN-ROSENTHAL DIABETIC HYPERTENSIVE RATS

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Abstract

Objective:

Hypertension and Diabetes commonly coexist and have been implicated in deterioration of kidneys, heart and impairment of pancreas. Empagliflozin (Empa), a selective SGLT2 inhibitor, is a new agent for treatment of diabetes via enhancing glucosuria, independent of insulin resistance. This study evaluates Empa's prophylactic beneficial effect on glomerular, cardiac and pancreatic integrity, in CRDH animals.

Design and method:

Cohen Rosenthal Diabetic Hypertensive rats (CRDH) were divided into 3 groups: A- Sugar diet (SD) + Empa, B-Sugar Diet + Veh, C-Regular Chow + Veh (Control). Drug was given for 4 months via drinking water at a dose of 10mg/kg/day. Hyperglycemia, hypertension, and additional biochemical parameters were monitored. Immunofluorescence analysis of glomerular nephrin and H&E in pancreas was performed in different experimental groups and their sham controls. To assess left ventricular (LV) remodeling and function, a special small animal echocardiography scanner was used.

Results:

Blood pressure was significantly (P < 0.05) reduced in Empa group (152 ± 5.1 mmHg) as compared with Veh (170.8 ± 5.9) and control groups (167.3 ± 6.9). Glucose levels were significantly reduced in treated vs. Veh group. Glucosuria and urine volume were dramatically increased in Empa group, while proteinuria was significantly reduced. Diabetic rats exhibited moderate disruption of slit diaphragm structure as seen by loss of nephrin. Beneficial effects of Empa were evident by preservation of nephrin, and subsequently reduction of proteinuria. Empa treatment prevented fatty infiltration and atrophy of exocrine pancreas, thus preserving pancreatic function. Finally, EMPA reduced adverse LV remodeling, indicated by change in LV mass (Fig.1), LV dilatation (6.6 ± 4.8 vs. 19.9 ± 4.9 vs 21.3 ± 2.9 %; p = 0.04), and improved cardiac contractility (3.7 ± 3.7 vs. −4.6 ± 13.1 vs −13.6 ± 5.1 %; p = 0.07), compared with control.

Conclusions:

Empa has additive beneficial effects by preventing diabetic/hypertensive induced adverse cardiac remodeling, as well as impairment of kidney function. Our findings provide mechanistic insight into the protective effect of Empa on type 2 diabetes associated with risk for cardiovascular events.

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