RESUMO
OBJECTIVES: It is known that the receptor for advanced glycation end products (RAGE) activation is involved in the pathogenesis of cardiovascular disease in diabetes. Previous studies have shown the presence of angiotensin II (Ang II) in diabetes, suggesting a role for this hormone during the disease. However, the association between RAGE and Ang II during pathologic cardiac remodelling after streptozotocin (STZ)-induced diabetes remains unclear. Because Ang II is capable of inducing pro-inflammatory events, blocking its production (enalapril), and its action on its receptor (losartan) could decrease inflammatory events in the myocardium in this experimental model of diabetes. Thus, the aim of this study was to assess the association between RAGE expression, inflammatory events and Ang II in the myocardium during STZ-induced diabetes. METHODS: Diabetes was induced by intravenous injection of STZ in Sprague-Dawley rats. Myocardial expressions of RAGE, monocyte/macrophage (ED-1-positive cells) infiltration and the intercellular adhesion molecule-1 were determined by histochemical methods. Levels of circulating endothelin-1 (ET-1) were determined by enzyme-linked immunoassay. Effects of Ang II included blocking using losartan (15 mg/kg body weight per day by gastric gavage) or enalapril (18 mg/kg body weight per day by gastric gavage). RESULTS: Increased expression of both RAGE and ED-1 was seen in the myocardium, but expression of myocardial vascular intercellular adhesion molecule-1 remained unchanged. Circulating levels of ET-1 in STZ rats were increased. Reninâangiotensin system inhibition decreased expression of myocardial RAGE, ED-1 and ET-1. CONCLUSIONS: The present findings suggest a role for Ang II in myocardial inflammation in STZ-induced diabetes mediated by RAGE and ET-1.
Assuntos
Angiotensina II/farmacologia , Diabetes Mellitus Experimental/metabolismo , Endotelina-1/metabolismo , Macrófagos/imunologia , Monócitos/imunologia , Miocárdio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Produtos Finais de Glicação Avançada/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Ratos , Ratos Sprague-Dawley , Vasoconstritores/farmacologiaRESUMO
This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.