Diego Barretti

Effects of Aerobic Exercise Training on Cardiac Renin-Angiotensin System in an Obese Zucker Rat Strain

Objective Obesity and renin angiotensin system (RAS) hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT) can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. Methods The rats were divided into the following groups: Lean Zucker rats (LZR); lean Zucker rats plus EXT (LZR+EXT); obese Zucker rats (OZR) and obese Zucker rats plus EXT (OZR+EXT). EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR), systolic blood pressure (SBP), cardiac hypertrophy (CH) and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. Results The resting HR decreased (∼12%) for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05), while a tendency was found for OZR versus OZR+EXT (p = 0.07). In addition, exercise reduced (57%) triglycerides and (61%) LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE) activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66%) and (42%), respectively, less angiotensin II (Ang II) plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. Conclusion Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

Anabolic steroid associated to physical training induces deleterious cardiac effects.

PURPOSE Cardiac aldosterone might be involved in the deleterious effects of nandrolone decanoate (ND) on the heart. Therefore, we investigated the involvement of cardiac aldosterone, by the pharmacological block of AT1 or mineralocorticoid receptors, on cardiac hypertrophy and fibrosis. METHODS Male Wistar rats were randomized into eight groups (n = 14 per group): Control (C), nandrolone decanoate (ND), trained (T), trained ND (TND), ND + losartan (ND + L), trained ND + losartan (TND + L), ND + spironolactone (ND + S), and trained ND + spironolactone (TND + S). ND (10 mg·kg(-1)·wk(-1)) was administered during 10 wk of swimming training (five times per week). Losartan (20 mg·kg(-1)·d(-1)) and spironolactone (10 mg·kg(-1)·d(-1)) were administered in drinking water. RESULTS Cardiac hypertrophy was increased 10% by using ND and 17% by ND plus training (P < 0.05). In both groups, there was an increase in the collagen volumetric fraction (CVF) and cardiac collagen type III expression (P < 0.05). The ND treatment increased left ventricle-angiotensin-converting enzyme I activity, AT1 receptor expression, aldosterone synthase (CYP11B2), and 11-β hydroxysteroid dehydrogenase 2 (11β-HSD2) gene expression and inflammatory markers, TGFβ and osteopontin. Both losartan and spironolactone inhibited the increase of CVF and collagen type III. In addition, both treatments inhibited the increase in left ventricle-angiotensin-converting enzyme I activity, CYP11B2, 11β-HSD2, TGFβ, and osteopontin induced by the ND treatment. CONCLUSIONS We believe this is the first study to show the effects of ND on cardiac aldosterone. Our results suggest that these effects may be associated to TGFβ and osteopontin. Thus, we conclude that the cardiac aldosterone has an important role on the deleterious effects on the heart induced by ND.

Exercise Training Restores Cardiac MicroRNA-1 and MicroRNA-29c to Nonpathological Levels in Obese Rats

We previously reported that aerobic exercise training (AET) consisted of 10 weeks of 60-min swimming sessions, and 5 days/week AET counteracts CH in obesity. Here, we evaluated the role of microRNAs and their target genes that are involved in heart collagen deposition and calcium signaling, as well as the cardiac remodeling induced by AET in obese Zucker rats. Among the four experimental Zucker groups: control lean rats (LZR), control obese rats (OZR), trained lean rats (LZR + TR), and trained obese rats (OZR + TR), heart weight was greater in the OZR than in the LZR group due to increased cardiac intramuscular fat and collagen. AET seems to exert a protective role in normalizing the heart weight in the OZR + TR group. Cardiac microRNA-29c expression was decreased in OZR compared with the LZR group, paralleled by an increase in the collagen volumetric fraction (CVF). MicroRNA-1 expression was upregulated while the expression of its target gene NCX1 was decreased in OZR compared with the LZR group. Interestingly, AET restored cardiac microRNA-1 to nonpathological levels in the OZR-TR group. Our findings suggest that AET could be used as a nonpharmacological therapy for the reversal of pathological cardiac remodeling and cardiac dysfunction in obesity.

Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training

Background. We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats. Results. Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2. Conclusion. Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders.

Exercise Training Restores the Cardiac Microrna-16 Levels Preventing Microvascular Rarefaction in Obese Zucker Rats

Objective: To evaluate the effects of aerobic exercise training (AET) on cardiac miRNA-16 levels and its target gene VEGF related to microvascular rarefaction in obese Zucker rats (OZR). Methods: OZR (n = 11) and lean (L; n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming exercise training lasted 60 min, 1×/day/10 weeks, with 4% body weight workload. Cardiac angiogenesis was assessed by histological analysis (periodic acid-Schiff) by calculating the capillary/fiber ratio. The protein expressions of VEGF, VEGFR2, and CD31 were evaluated by western blot. The expression of miRNA-16 was evaluated by real-time PCR. Results: Heart rate decreased in the trained groups compared to sedentary groups. The cardiac capillary/fiber ratio was reduced in OZR compared to L, LT and OZRT groups, indicating that aerobic exercise training (AET) was capable of reversing the microvascular rarefaction in the obese animals. miRNA-16 expression was increased in OZR compared to L, LT and OZRT. In contrast, its target, VEGF protein expression was 24% lower in OZR compared to L group, which has been normalized in OZRT group. VEGFR2 protein expression was increased in trained groups compared to their controls. CD31, a endothelial cells marker, showed increased expression in OZRT compared to OZR, indicating greater vascularization in OZRT group. Conclusion: AET induced cardiac angiogenesis in obese animals. This revascularization is associated with a decrease in miRNA-16 expression permissive for increased VEGF protein expression, suggesting a mechanism for potential therapeutic application in vascular diseases.

O papel do esteroide anabolizante sobre a hipertrofia e força muscular em treinamentos de resistência aeróbia e de força

INTRODUCAO: Os efeitos dos esteroides anabolizantes (EA) sobre a massa muscular e forca sao controversos e dependentes do treinamento realizado e das fibras musculares recrutadas. Com isso, o objetivo deste estudo foi avaliar os efeitos da associacao de EA ao treinamento de forca ou aerobio sobre a hipertrofia e forca muscular. METODOS: Ratos Wistar (42) foram divididos em seis grupos: sedentario (SC, n = 7), sedentario anabolizante (SA, n = 7), treinado natacao controle (TNC, n = 7), treinado natacao anabolizante (TNA, n = 7), treinado forca controle (TFC, n = 7) e treinado forca anabolizante (TFA, n = 7). O EA foi administrado duas vezes por semana (10mg/kg/semana). Os protocolos de treinamento foram realizados durante 10 semanas, cinco sessoes semanais. Foram avaliadas a hipertrofia dos musculos soleo, plantar e gastrocnemio (massa muscular corrigida pelo comprimento da tibia), a proteina total muscular (Bradford) e a forca muscular em patas traseiras (testes de resistencia a inclinacao). RESULTADOS: Nao foram observadas diferencas significantes na hipertrofia do musculo soleo. Os grupos TFC e TFA apresentaram, respectivamente, hipertrofia de 18% e 31% no musculo plantar comparado ao grupo SC. A hipertrofia foi 13% maior no grupo TFA em relacao ao grupo TFC. Resultados semelhantes foram encontrados no musculo gastrocnemio. Os grupos TFC e TFA apresentaram significantes aumentos na quantidade total de proteina nos musculos plantares, sendo essa mais pronunciada no grupo TFA e positivamente correlaciona a hipertrofia muscular. Observamos aumento de forca nas patas traseiras nos grupos TCF e TAF. CONCLUSAO: A administracao de EA ou sua associacao ao treinamento aerobio nao aumenta a massa muscular e forca. Porem, a associacao ao treinamento de forca leva a maior hipertrofia muscular em fibras glicoliticas. Portanto, o tipo de treinamento fisico, recrutamento muscular e caracteristicas das fibras musculares, parecem ter importante impacto sobre as respostas anabolicas induzidas pelo EA

Corrigendum to “Exercise Training Restores Cardiac MicroRNA-1 and MicroRNA-29c to Nonpathological Levels in Obese Rats”

[This corrects the article DOI: 10.1155/2017/1549014.].

Treinamento físico aeróbio previne à hipertrofia cardíaca patológica e melhora a função diastólica em ratos Zucker obesos

A obesidade e uma patologia diretamente relacionada com o desenvolvimento de doencas cardiovasculares. Por outro lado, o treinamento fisico aerobio atenua o desenvolvimento da obesidade e promove beneficios cardiacos em obesos. Dessa forma, nosso objetivo foi investigar se a obesidade altera a funcao cardiaca e se sua associacao com o treinamento fisico aerobio promove melhora na funcao cardiaca em ratos Zucker obesos. Os ratos Zucker foram divididos da seguinte forma: grupo magro (GM), grupo obeso (GO), grupo magro treinado (GMTR) e grupo obeso treinado (GOTR). O protocolo de treinamento aerobio de natacao foi realizado por um periodo de 10 semanas com cinco sessoes semanais de 60 minutos de duracao. A frequencia cardiaca de repouso, a pressao arterial sistolica, a hipertrofia e funcao cardiaca foram avaliadas no final do periodo de treinamento fisico. Ambos os grupos treinados apresentaram uma queda de 12% da frequencia cardiaca de repouso, quando comparado com seus respectivos controles. Ainda, nossos resultados demonstraram que o treinamento aerobio reduziu o aumento da massa cardiaca em 13% e melhorou a funcao diastolica na obesidade em 43%. Em conclusao, nossos dados demonstraram que o treinamento fisico aerobio reverteu os prejuizos cardiacos causados pela obesidade.