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Resumo Fundamento O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco. Objetivo Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica. Métodos Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p

Resistance training (RT) improves the cardiomyocyte calcium (Ca2+) cycling during excitation-contraction coupling. However, the role of RT in cardiomyocyte contractile function associated with Ca2+ handling in obesity is unclear. Wistar rats were distributed into four groups: control, sedentary obese, control plus RT, and obesity plus RT. The 10-wk RT protocol was used (4-5 vertical ladder climbs, 60-second interval, 3× a week, 50-100% of maximum load). Metabolic, hormonal, cardiovascular and biochemical parameters were determined. Reduced leptin levels, epididymal, retroperitoneal and visceral fat pads, lower body fat, and adiposity index were observed in RT. Obesity promoted elevation of collagen, but RT did not promote modifications of LV collagen in ObRT. RT induced elevation in maximum rates of contraction and relaxation, and reduction of time to 50% relaxation. ObRT group did not present improvement in the cardiomyocyte contractile function in comparison to Ob group. Reduced cardiac PLB serine16 phosphorylation (pPLB Ser16) and pPLB Ser16/PLB ratio with no alterations in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and phospholamban (PLB) expression were observed in Ob groups. Resistance training improved body composition reduced fat pads and plasma leptin levels but did not promote positive alterations in cardiomyocyte contractile function, Ca2+ handling and phospholamban phosphorylation.

Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling.To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis.Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p0.05.Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger.Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco.Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica.Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p0,05.Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+.Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.

Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.

Several diseases are associated with excess of adipose tissue, and obesity is considered an independent risk factor for the development of cardiac remodeling and heart failure. Dietary aspects have been studied to elucidate the mechanisms involved in these processes. Thus, the purpose was the development and characterization of an obesity experimental model from hypercaloric diets, which resulted in cardiac remodeling and predisposition to heart failure. Thirty- day-old male Wistar rats (n = 52) were randomized into four groups: control (C), high sucrose (HS), high-fat (HF) and high-fat and sucrose (HFHS) for 20 weeks. General characteristics, comorbidities, weights of the heart, left (LV) and right ventricles, atrium, and relationships with the tibia length were evaluated. The LV myocyte cross sectional area and fraction of interstitial collagen were assayed. Cardiac function was determined by hemodynamic analysis and the contractility by cardiomyocyte contractile function. Heart failure was analyzed by pulmonary congestion, right ventricular hypertrophy, and hemodynamic parameters. HF and HFHS models led to obesity by increase in adiposity index (C = 8.3 ± 0.2% vs. HF = 10.9 ± 0.5%, HFHS = 10.2 ± 0.3%). There was no change in the morphological parameters and heart failure signals. HF and HFHS caused a reduction in times to 50% relaxation without cardiomyocyte contractile damage. The HS model presented cardiomyocyte contractile dysfunction visualized by lower shortening (C: 8.34 ± 0.32% vs. HS: 6.91 ± 0.28), as well as the Ca2+ transient amplitude was also increased when compared to HFHS. In conclusion, the experimental diets based on high amounts of sugar, lard or a combination of both did not promote cardiac remodeling with predisposition to heart failure under conditions of obesity or excess sucrose. Nevertheless, excess sucrose causes cardiomyocyte contractility dysfunction associated with alterations in the myocyte sensitivity to intracellular Ca2+.

Background: Dietary interventions in rodents can induce an excess of adipose tissue and metabolic disorders that resemble human obesity. Nevertheless, these approaches are not standardized, and the phenotypes may vary distinctly among studies. The aim of this study was to investigate the effects of different dietary interventions on nutritional, metabolic, biochemical, hormonal, and cardiovascular profiles, as well as to add to development and characterization of an experimental model of obesity. Methods: Male Wistar rats were randomized into four groups: control diet (C), high-sugar (HS), high-fat (HF), or high-sugar and high-fat (HFHS). Weekly measurements of body weight, adiposity, area under the curve (AUC) for glucose, blood pressure (BP) and serum triglycerides, total cholesterol level, and leptin were performed. Results: HF and HFHS models were led to obesity by increases in adipose tissue deposition and the adiposity index. All hypercaloric diets presented systolic BP increases. In addition, the AUC for glucose was greater in HF and HFHS than in C, and only the HF group presented hyperleptinemia. Conclusions: HF and HFHS diet approaches promote obesity and comorbidities, and thus represent a useful tool for studying human obesity-related disorders. By contrast, the HS model did not prove to be a good model of obesity.