Effects of AT1 receptor antagonism on interstitial and ultrastructural remodeling of heart in response to a hypercaloric diet

摘要

Palatable hypercaloric feeding has been associated with angiotensin‐II type 1 receptor (AT1R) stimulation and cardiac remodeling. This study analyzed whether AT1R antagonism attenuates cardiac remodeling in rats subjected to a palatable hypercaloric diet. Male Wistar‐Kyoto rats were subjected to a commercial standard rat chow (CD) or a palatable hypercaloric diet (HD) for 35 weeks and then allocated into four groups: CD, CL, HD, and HL; L groups received losartan in drinking water (30 mg/kg/day) for 5 weeks. Body weight, adiposity, and glycemia were evaluated. The cardiovascular study included echocardiography, and myocardial morphometric and ultrastructural evaluation. Myocardial collagen isoforms Type I and III were analyzed by Western blot. Both HD and HL had higher adiposity than their respective controls. Cardiomyocyte cross‐sectional‐area (CD 285 ± 49; HD 344 ± 91; CL 327 ± 49; HL 303 ± 49 μm²) and interstitial collagen fractional area were significantly higher in style="fixed-case">HD than style="fixed-case">CD and unchanged by losartan. style="fixed-case">HD showed marked ultrastructural alterations such as myofilament loss, and severe mitochondrial swelling. style="fixed-case">CL presented higher Type I collagen expression when compared to style="fixed-case">CD and style="fixed-case">HL groups. The ultrastructural changes and type I collagen expression were attenuated by losartan in style="fixed-case">HL. Losartan attenuates systolic dysfunction and ultrastructural abnormalities without changing myocardial interstitial remodeling in rats subjected to a palatable hypercaloric diet.