RESUMEN
It has been described that the cardiac dysfunction in the obesity model is because of collagen imbalance and that angiotensin II (Ang II) contributes to myocardial fibrosis. However, it remains undefined if changes in collagen I and III metabolism in obesity is due to the renin-angiotensin system (RAS) dysregulation from myocardium or excessive adipose tissue. AIM: This study aimed to verify whether the changes in myocardial collagen metabolism result from RAS deregulation of cardiac or adipose tissue in an obesity model. MAIN METHODS: Wistar rats were fed with control (CD) and high-fat (HFD) diets for 30 weeks. After the dietary intervention, animals were assigned to be treated with losartan at the 30 mg/kg/day dosage or kept untreated for an additional five weeks. KEY FINDINGS: HFD induced obesity, comorbidities, and cardiac collagen overexpression. The HFD group presented an increase in Ang II levels in both adipose tissue and plasma, as well as AT1 receptor expression in cardiac tissue. Of note, the myocardial Ang II was not changed in the HFD group. Losartan administration reduced some obesity-induced comorbidities regardless of weight loss. The AT1 receptor blockade also decreased the release of Ang II from adipose tissue and myocardial AT1 receptor and collagen. SIGNIFICANCE: It was seen that excessive adipose tissue is responsible for the exacerbated circulating Ang II, which induced cardiac fibrosis development.
Asunto(s)
Tejido Adiposo/metabolismo , Angiotensina II/metabolismo , Miocardio/patología , Obesidad/fisiopatología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Dieta Alta en Grasa/efectos adversos , Fibrosis , Losartán/farmacología , Masculino , Miocardio/metabolismo , Ratas , Ratas Wistar , Sistema Renina-Angiotensina/fisiologíaRESUMEN
Severe food restriction (FR) impairs cardiac performance, although the causative mechanisms remain elusive. Since proteins associated with calcium handling may contribute to cardiac dysfunction, this study aimed to evaluate whether severe FR results in alterations in the expression and activity of Ca2+-handling proteins that contribute to impaired myocardial performance. Male 60-day-old Wistar-Kyoto rats were fed a control or restricted diet (50% reduction in the food consumed by the control group) for 90 days. Body weight, body fat pads, adiposity index, as well as the weights of the soleus muscle and lung, were obtained. Cardiac remodeling was assessed by morphological measures. The myocardial contractile performance was analyzed in isolated papillary muscles during the administration of extracellular Ca2+ and in the absence or presence of a sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) specific blocker. The expression of Ca2+-handling regulatory proteins was analyzed via Western Blot. Severe FR resulted in a 50% decrease in body weight and adiposity measures. Cardiac morphometry was substantially altered, as heart weights were nearly twofold lower in FR rats. Papillary muscles isolated from FR hearts displayed mechanical dysfunction, including decreased developed tension and reduced contractility and relaxation. The administration of a SERCA2a blocker led to further decrements in contractile function in FR hearts, suggesting impaired SERCA2a activity. Moreover, the FR rats presented a lower expression of L-type Ca2+ channels. Therefore, myocardial dysfunction induced by severe food restriction is associated with changes in the calcium-handling properties in rats.
Asunto(s)
Señalización del Calcio , Calcio/metabolismo , Restricción Calórica , Cardiopatías/etiología , Desnutrición/complicaciones , Mitocondrias Cardíacas/metabolismo , Contracción Miocárdica , Miocitos Cardíacos/metabolismo , Músculos Papilares/metabolismo , Adiposidad , Animales , Canales de Calcio Tipo L/metabolismo , Modelos Animales de Enfermedad , Cardiopatías/metabolismo , Cardiopatías/patología , Cardiopatías/fisiopatología , Masculino , Desnutrición/metabolismo , Desnutrición/patología , Desnutrición/fisiopatología , Mitocondrias Cardíacas/patología , Miocitos Cardíacos/patología , Músculos Papilares/patología , Músculos Papilares/fisiopatología , Ratas Endogámicas WKY , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Pérdida de PesoRESUMEN
BACKGROUND: Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. OBJECTIVE: To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. METHODS: Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). RESULTS: There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). CONCLUSION: GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.
Asunto(s)
Hormona del Crecimiento/farmacología , Entrenamiento de Fuerza/métodos , Remodelación Ventricular/efectos de los fármacos , Animales , Peso Corporal , Calcio/metabolismo , Proteínas de Unión al Calcio/análisis , Colágeno/análisis , Colágeno/efectos de los fármacos , Forma BB de la Creatina-Quinasa/sangre , Forma BB de la Creatina-Quinasa/efectos de los fármacos , Expresión Génica , Ventrículos Cardíacos/efectos de los fármacos , Masculino , Miocitos Cardíacos/efectos de los fármacos , Tamaño de los Órganos , Reacción en Cadena de la Polimerasa , Ratas Wistar , Rianodina/análisis , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/análisis , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/efectos de los fármacos , Factores de Tiempo , Remodelación Ventricular/genéticaRESUMEN
Obesity has been shown to impair myocardial performance. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them beta-adrenergic (ßA) system, an important mechanism of regulation of myocardial contraction and relaxation. The objective of present study was to evaluate the involvement of ßA system components in myocardial dysfunction induced by obesity. Thirty-day-old male Wistar rats were distributed in control (C, n = 25) and obese (Ob, n = 25) groups. The C group was fed a standard diet and Ob group was fed four unsaturated high-fat diets for 15 weeks. Cardiac function was evaluated by isolated papillary muscle preparation and ßA system evaluated by using cumulative concentrations of isoproterenol and Western blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats and several comorbidities; however, were not associated with changes in systolic blood pressure. Obesity caused structural changes and the myocardial responsiveness to post-rest contraction stimulus and increased extracellular calcium (Ca2+) was compromised. There were no changes in cardiac function between groups after ßA stimulation. The obesity was not accompanied by changes in protein expression of G protein subunit alpha (Gsα) and ßA receptors (ß1AR and ß2AR). In conclusion, the myocardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to ßAR system impairment at the receptor-signalling pathway.
Asunto(s)
Corazón/fisiopatología , Obesidad/fisiopatología , Músculos Papilares/fisiopatología , Receptores Adrenérgicos beta/metabolismo , Adiposidad/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Western Blotting , Calcio/farmacología , Dieta Alta en Grasa/efectos adversos , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Corazón/efectos de los fármacos , Isoproterenol/farmacología , Masculino , Contracción Miocárdica/efectos de los fármacos , Obesidad/etiología , Obesidad/metabolismo , Músculos Papilares/efectos de los fármacos , Músculos Papilares/metabolismo , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.