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

• Published in: Physiological reports 2019-01, Vol.7 (1), p.e13964-n/a
• Main Authors: Oliveira‐Junior, Silvio A., Dal Pai, Maeli, Guizoni, Daniele M., Torres, Barbara P., Martinez, Paula F., Campos, Dijon H. S., Okoshi, Marina P., Okoshi, Katashi, Padovani, Carlos R., Cicogna, Antonio C.
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue and Obesity; Angiotensin; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Arterial Pressure; Blood glucose; Blood Pressure; Body weight; Cardiac Remodeling; Cardiomyocytes; Cardiovascular Physiology; Collagen; Collagen (type I); Collagen - genetics; Collagen - metabolism; Diet; Diet, High-Fat - adverse effects; Drinking water; Echocardiography; Heart; High‐Fat Diet; Isoforms; Losartan - pharmacology; Male; Mitochondria; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Nutrition; Original Research; Physiology; Rats; Rats, Wistar; Ultrastructure; Ventricular Dysfunction - etiology; Ventricular Dysfunction - metabolism; Ventricular Dysfunction - pathology; Ventricular Remodeling
• ISSN: 2051-817X
• DOI: 10.14814/phy2.13964

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 HD than CD and unchanged by losartan. HD showed marked ultrastructural alterations such as myofilament loss, and severe mitochondrial swelling. CL presented higher Type I collagen expression when compared to CD and HL groups. The ultrastructural changes and type I collagen expression were attenuated by losartan in HL. Losartan attenuates systolic dysfunction and ultrastructural abnormalities without changing myocardial interstitial remodeling in rats subjected to a palatable hypercaloric diet. Diet reduced type I collagen expression in the heart. The ultrastructural changes and type I collagen expression promoted by high‐fat and hypercaloric diet were attenuated by AT1 antagonism.