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J Cardiovasc Pharmacol Ther ; 23(4): 358-371, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29627992

RESUMO

The effectiveness of empagliflozin (EMPA), a sodium glucose cotransporter type 2 inhibitor, on the kidney, pancreas, and heart was investigated in the Cohen Rosenthal diabetic hypertensive rat model (CRDH rat). Six-week-old CRDH male rats were fed a sugar diet (SD) and treated with the compound EMPA (group Drug/SD) or respective comparator with vehicle (group Veh/SD). A control group was fed a regular diet without treatment (group Veh/P). Preventive treatment with EMPA was measured during 4 months of follow-up. The treatment effect was evaluated according to results observed after 4 months in group Drug/SD when compared to those in group Veh/SD. Significant effect resulted in the following parameters: enhancement of urinary glucose excretion in association with diuresis; amelioration of postprandial hyperglycemia and fasting blood glucose levels; and decrease in calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as well as lower systolic and diastolic blood pressures. At the end of treatment, EMPA preserved nephrin integrity in the kidney, reduced proteinuria, and prevented diabetes-induced damage to glomerular diaphragm structure. In the pancreas, EMPA demonstrated an impressive decrease in fatty infiltration and atrophy. Blood pressure was significantly reduced in the EMPA-treated group (15 ± 5.1 mm Hg, P < .05) in contrast to the vehicle and control groups. Finally, compared to controls, EMPA significantly reduced left ventricle (LV) mass and LV systolic dilatation, according to 2-dimensional echocardiography. The importance of the study lies in demonstrating the efficacy of an antidiabetic drug with beneficial effects on blood pressure, weight, kidney, and pancreas and a positive effect on the heart.


Assuntos
Compostos Benzidrílicos/farmacologia , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Glucosídeos/farmacologia , Hipertensão/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/fisiopatologia , Modelos Animais de Doenças , Homeostase , Hipertensão/sangue , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Resistência à Insulina , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Proteinúria/sangue , Proteinúria/fisiopatologia , Proteinúria/prevenção & controle , Ratos Endogâmicos SHR , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle
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