Vander José das Neves

Proatherosclerotic effects of chronic stress in male rats: Altered phenylephrine sensitivity and nitric oxide synthase activity of aorta and circulating lipids

The aim of this study was to analyze the effects of chronic mild unpredictable stress (CMS) on the vasoconstrictor response and morphology of the thoracic aorta and serum lipid profiles in rats. Male Sprague–Dawley rats were submitted to CMS, which consisted of the application of different stressors for 7 days per week across 3 weeks. The rats were sacrificed 15 days after CMS expsoure. CMS induced supersensitivity to the vasoconstrictor effect of phenylephrine in endothelium-intact thoracic aortic rings without changes in aortic rings without endothelium, or pre-incubated with nitric oxide (NO) synthesis inhibitor. Rats submitted to CMS showed hypertrophy of the intima and tunica media of thoracic aorta, increased serum levels of triglycerides, total cholesterol, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and atherogenic index, without changes in high-density lipoprotein cholesterol levels, when compared with control rats. These data indicate that CMS induces physiological and morphological changes that may contribute to the development of atherosclerosis by mechanisms related to deficiency in NO production and dyslipidemia.

Exercise training in hypertension: Role of microRNAs.

Hypertension is a complex disease that constitutes an important public health problem and demands many studies in order to understand the molecular mechanisms involving his pathophysiology. Therefore, an increasing number of studies have been conducted and new therapies are continually being discovered. In this context, exercise training has emerged as an important non-pharmacological therapy to treat hypertensive patients, minimizing the side effects of pharmacological therapies and frequently contributing to allow pharmacotherapy to be suspended. Several mechanisms have been associated with the pathogenesis of hypertension, such as hyperactivity of the sympathetic nervous system and renin-angiotensin aldosterone system, impaired endothelial nitric oxide production, increased oxygen-reactive species, vascular thickening and stiffening, cardiac hypertrophy, impaired angiogenesis, and sometimes genetic predisposition. With the advent of microRNAs (miRNAs), new insights have been added to the perspectives for the treatment of this disease, and exercise training has been shown to be able to modulate the miRNAs associated with it. Elucidation of the relationship between exercise training and miRNAs in the pathogenesis of hypertension is fundamental in order to understand how exercise modulates the cardiovascular system at genetic level. This can be promising even for the development of new drugs. This article is a review of how exercise training acts on hypertension by means of specific miRNAs in the heart, vascular system, and skeletal muscle.

Nandrolone and resistance training induce heart remodeling Role of fetal genes and implications for cardiac pathophysiology

AIMS This study was conducted to assess the isolated and combined effects of nandrolone and resistance training on cardiac morphology, function, and mRNA expression of pathological cardiac hypertrophy markers. MAIN METHODS Wistar rats were randomly divided into four groups and submitted to 6 weeks of treatment with nandrolone and/or resistance training. Cardiac parameters were determined by echocardiography. Heart was analyzed for collagen infiltration. Real-time RT-PCR was used to assess the pathological cardiac hypertrophy markers. KEY FINDINGS Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased the cardiac collagen content, and reduced the cardiac index in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the ratio of maximum early to late transmitral flow velocity in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the alpha-myosin heavy chain gene expression in both non-trained and trained groups, when compared with the respective vehicle-treated groups. Training reduced the beta-myosin heavy chain gene expression in the groups treated with vehicle and nandrolone. Only the association between training and nandrolone increased the expression of the skeletal alpha-actin gene and atrial natriuretic peptide in the left ventricle. SIGNIFICANCE This study indicated that nandrolone, whether associated with resistance training or not, induces cardiac hypertrophy, which is associated with enhanced collagen content, re-expression of fetal genes the in left ventricle, and impaired diastolic and systolic function.

Chronic stress, but not hypercaloric diet, impairs vascular function in rats

The aim of this study was to evaluate vascular and metabolic effects of chronic mild unpredictable stress (CMS) and hypercaloric diet (HD) without carbohydrate supplementation in rats. Male Sprague-Dawley rats were randomly assigned to four groups: Control, HD, CMS, and HD plus CMS. CMS consisted of the application of different stressors for 3 weeks. The rats were killed 15 days after CMS exposure. The HD group presented higher plasma lipid concentrations, without changes in fasting glucose concentration, glucose tolerance test, and vascular function and morphology, in comparison with the control group. Stressed rats presented higher fasting blood concentration of insulin, higher homeostasis model assessment index values and area under the curve in an oral glucose tolerance test, in comparison with non-stressed rats. CMS increased the plasma concentrations of corticosterone and lipids, and the atherogenic index values, without change in high-density lipoprotein level. CMS increased intima-media thickness and induced endothelium-dependent supersensitivity to phenylephrine, and lowered the relaxation response to acetylcholine in the thoracic aorta isolated from rats fed with control or HD, in comparison with non-stressed groups. CMS effects were independent of diet. In non-stressed rats, the HD induced dyslipidemia, but did not change glucose metabolism, vascular function, or morphology. The data from this study indicate that CMS promotes a set of events which together can contribute to impair function of the thoracic aorta.

Effects of nandrolone and resistance training on the blood pressure, cardiac electrophysiology, and expression of atrial β-adrenergic receptors

AIMS This study was performed to assess isolated and combined effects of nandrolone and resistance training on the blood pressure, cardiac electrophysiology, and expression of the β1- and β2-adrenergic receptors in the heart of rats. MAIN METHODS Wistar rats were randomly divided into four groups and submitted to a 6-week treatment with nandrolone and/or resistance training. Cardiac hypertrophy was accessed by the ratio of heart weight to the final body weight. Blood pressure was determined by a computerized tail-cuff system. Electrocardiography analyses were performed. Western blotting was used to access the protein levels of the β1- and β2-adrenergic receptors in the right atrium and left ventricle. KEY FINDINGS Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased systolic blood pressure depending on the treatment time. Resistance training decreased systolic, diastolic and mean arterial blood pressure, as well as induced resting bradycardia. Nandrolone prolonged the QTc interval for both trained and non-trained groups when they were compared to their respective vehicle-treated one. Nandrolone increased the expression of β1- and β2-adrenergic receptors in the right atrium for both trained and non-trained groups when they were compared to their respective vehicle-treated one. SIGNIFICANCE This study indicated that nandrolone, associated or not with resistance training increases blood pressure depending on the treatment time, induces prolongation of the QTc interval, and increases the expression of β1- and β2-adrenergic receptors in the cardiac right atrium, but not in the left ventricle.

Unraveling the role of high-intensity resistance training on left ventricle proteome: Is there a shift towards maladaptation?

UNLABELLED High-intensity resistance training (RT) induces adaptations that improve physiological function. However, high intensity, volume and/or frequency may lead to injury and other health issues such as adverse cardiac effects. The aim of this study was to evaluate the effect of RT on left ventricle proteome, and to identify the pathways involved on the harmful adaptations induced by this protocol. Male Wistar rats were randomized into 2 groups: Trained (T) and Sedentary (S). Animals from T group were trained for 6weeks, and then all the animals were sacrificed and left ventricle was isolated for analysis. We identified 955 proteins, and 93 proteins were considered; 36 were expressed exclusively in T group, and 4 in S group. Based on quantitative analysis, 42 proteins were found overexpressed and 11 underexpressed in T group compared with S group. Using the Gene Ontology to relate the biological processes in which these proteins are involved, we conclude that RT protocol promotes changes similar to those found in the initial phase of heart failure, but we also observed a concomitant increased expression of protective proteins, suggesting the activation of pathways to avoid major damages on left ventricle and delay the onset of pathological hypertrophy. STATEMENT OF SIGNIFICANCE OF THE STUDY Our study shows that high-intensity RT protocol changes left ventricle proteome, modifying metabolic profile of heart tissue and inducing the expression of proteins that acts against cardiac injury. We hypothesize that these adaptations occur to prevent the onset of cardiac dysfunction. Despite highly significant, it remains to be determined whether these adaptations are sufficient to further keep left ventricle function and exert cardioprotection, and whether this panel will be shifted towards maladaptation, and heart failure.

Dyslipidemia Induced by Stress

The pioneering work of Hans Selye (1936) led to the use of the word “stress” in a biological context gaining popularity world-wide. Stress is as an organic response to stressors that can be aversive stimuli or unknown situations capable of compromising homeostasis. During the stress reaction, the sympathetic nervous system and hypothalamic–pituitary–adrenal axis are stimulated. Consequently, serum concentrations of classical stress hormones, namely catecholamines and glucocorticoids, are increased and act on cells and tissues inducing adaptive changes in order to protect the organism and allow its survival. In addition, the stress reaction can also modulate immune system activities and the secretion of other hormones (gonadotrophins, estrogen, testosterone, thyroid, angiotensins). Considering that organic homeostatic systems are subject to frequent environmental and internal variations, Sterling and Eyer (1988) proposed the term alostasis to describe the adaptative processes that actively maintain stability through physiological changes. The terms eustress and efficient allostasis describe facile adaptation, such as a quick peak stress response to mobilize energy to deal with an acute stressor, and a rapid return to baseline, when the stressor terminates. On the other hand, distress or allostatic load refers to an imbalance in systems that promote adaptation (Epel, 2009; Korte et al., 2005). This imbalance can simply be the result of too much repeated stress, but it can also be the result of adaptative systems that are out of balance and fail to shut-off or, alternatively, systems that fail to return to normal (Epel, 2009). Therefore the shut-off of the stress response is particularly important, because, when systems do not shut off in time, they can cause damage or promote pathology (McEwen, 1998). The classical stress hormones, glucocorticoids (cortisol) and catecholamines (epinephrine and norepinephrine), are catabolic and modulate the breakdown of glycogen, triglycerides and proteins into molecules that can be rapidly metabolized in order to generate energy (Black, 2002). These responses enable energy substrates to be directed to organs and tissues

Nandrolone combined with strenuous resistance training reduces vascular nitric oxide bioavailability and impairs endothelium-dependent vasodilation

HighlightsNandrolone plus strenuous RT impairs acetylcholine‐mediated aorta vasodilation.Nandrolone plus strenuous RT increased reactive species of oxygen levels.Nandrolone plus strenuous RT dramatically reduced vascular NO bioavailability.Nandrolone plus strenuous RT increased arterial wall thickness.Combination of nandrolone and strenuous RT might lead endothelial dysfunction. ABSTRACT Anabolic Androgenic Steroids (AASs) misuse has increased among adolescents and recreational athletes due to their potential effects on muscle hypertrophy. On the other hand, AAS might induce alterations on cardiovascular system, although some controversies regarding AAS on vascular properties remain unknown. To address this question, we aimed to investigate the effects of high doses of nandrolone combined with strenuous resistance training (RT) on function and structure of thoracic aorta. Rats were randomized into four groups: non‐trained vehicle (NTV), trained vehicle (TV), non‐trained nandrolone (NTN), and trained nandrolone (TN), and submitted to 6 weeks of treatment with nandrolone (5 mg/kg, twice a week) and/or resistance training. In vitro response of thoracic aorta to acetylcholine (ACh) was analyzed. Vascular nitric oxide (NO) and reactive oxygen species (ROS) synthesis were evaluated using 4,5‐diaminofluorescein diacetate (DAF‐2) and hydroethidine fluorescent techniques, respectively. Thoracic aorta was processed for microscopy analyses and tunica media thickness was measured. ACh‐mediated relaxation response was impaired in endothelium intact aortic rings isolated from trained rats (TV and TN) as compared with their matched non‐trained groups. TN rats showed reduced ACh‐mediated vasodilatation than NTN rats. NO production and bioavailability decreased in thoracic aorta of nandrolone‐treated rats in relation to their matched non‐trained group (NTN vs. NTV; TN vs. TV). ROS production and tunica media thickness were increased in TN rats when compared with TV rats. These findings indicate that high doses of nandrolone combined with strenuous RT affect NO bioavailability and might induce endothelial dysfunction and arterial morphological alterations.