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

Abstract

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.

Bloqueio de Receptores AT1 Melhora o Desempenho Funcional Miocárdico na Obesidade

“…[6][7][8] Feeding efficiency was obtained from the relationship between body weight variation and total energy intake. [6][7][8] Body weight was measured weekly, while weight gain was obtained from the difference between initial and final body weight values. Adipose tissue from the retroperitoneal, epididymal, and visceral regions was used to determine body fat content.…”

“…Adipose tissue from the retroperitoneal, epididymal, and visceral regions was used to determine body fat content. [6][7][8][9][10][11][12] Myocardial performance was assessed by in vitro study with papillary muscle isolated from LV. 7,16,18,29 After 20 weeks, animals were submitted to intraperitoneal anesthesia with ketamine hydrochloride (80 mg/kg), xylazine (5 mg/kg), and euthanasia.…”

“…3 Clinical studies have shown obesity may cause morphological and functional changes in the heart. 4,5 Moreover, experimental research proved this condition is associated with myocardial hypertrophy, [6][7][8] interstitial fibrosis, 8,9 and several molecular changes. 10,11 These responses include disorders in expression and functioning of peptides involved with intracellular calcium handling during muscle contraction and relaxation.…”