Maria José Costa Sampaio Moura

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.

Influence of anabolic steroid on anxiety levels in sedentary male rats.

The aim of this study was to evaluate the influence of nandrolone decanoate on anxiety levels in rats. Male Wistar rats were treated with nandrolone decanoate (5mg/kg, two times per week, i.m.) or vehicle (propylene glycol—0.2 ml/kg, two times per week, IM) for 6 weeks. Control rats were subject only to procedures related to their routine husbandry. By the end of 6 weeks, all groups (24–29 rats/group) were submitted to the elevated plus maze test in order to evaluate their anxiety level. Some of these animals (12– 14/group) were treated with diazepam (1 mg/kg i.p.) 30 min before the elevated plus maze test. Nandrolone decanoate significantly decreased the percentage of time spent in the open arms (1.46 ± 0.49%) compared with control (3.80 ± 0.97%) and vehicle (3.96 ± 0.85%) groups, with no difference between control and vehicle treatments. The percentage of open arm entries was also reduced in the group treated with nandrolone decanoate in comparison with the vehicle and control. No changes in the number of closed arm entries were detected. Diazepam abolished the effects of nandrolone decanoate on the percentage of time in, and entries into the open arms. The present study showed that chronic treatment with a high dose of nandrolone decanoate increased the anxiety level in male rats.

Atrial supersensitivity to noradrenaline in stressed female rats

Stress can change the responses to catecholamines in many tissues. The aim of this study was to investigate the influence of the estrous cycle on the sensitivity of right atria to noradrenaline in female rats subjected to acute swimming stress. Female Wistar rats in proestrus, estrus, metestrus or diestrus were submitted to a 50 min-swimming session. Immediately after the exercise, the rats were killed and their right atria were mounted for isometric recording of the spontaneous beating rate. Concentration-effect curves to noradrenaline were obtained before and after the inhibition of neuronal uptake with phenoxybenzamine (10 microM) and of extraneuronal uptake with estradiol (5 microM). Acute swimming stress did not change the right atrial sensitivity to noradrenaline in rats in estrus, metestrus and diestrus. However, swimming stress produced supersensitivity to noradrenaline in proestrus (pD(2) control: 7.14 +/- 0.03 vs. pD(2) swimming: 7.55 +/- 0.04; p<0.05). This supersensitivity was still observed after uptake inhibition. When catecholamine uptake was inhibited, the concentration-effect curve to noradrenaline was shifted to the left 2.5-fold in the proestrus control group and 1.7-fold in the proestrus stress group (p<0.05). In conclusion, the estrous cycle influenced the acute stress-induced atrial supersensitivity to noradrenaline.

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.

Influence of estradiol and progesterone on the sensitivity of rat thoracic aorta to noradrenaline

The aim of this study was to investigate the effects of low and high doses of estradiol, and of progesterone on the response to noradrenaline in rat thoracic aorta. Two weeks after bilateral ovariectomy, female rats received a s.c. injection of vehicle (corn oil, 0.1 mL/day), estradiol (10 microg/kg/day or 4 mg/kg/day) and/or progesterone (20 mg/kg/day), for eight days. On the ninth day, the rats were sacrificed and aortic rings, with or without endothelium, were used to generate concentration-response curves to noradrenaline. Aortic rings with intact endothelium from the high-dose (4 mg/kg/day) estradiol group were supersensitive to noradrenaline compared to the vehicle or low-dose (10 microg/kg/day) estradiol groups (pD2 values = 7.86+/-0.09, 7.30+/-0.11 and 7.35+/-0.04, respectively). Endothelium-intact aortic rings from high-estradiol rats were supersensitive to noradrenaline when compared to vehicle-, progesterone- and progesterone + high-estradiol-treated rats (pD2 values = 7.77+/-0.12, 7.21+/-0.13, 6.93+/-0.04 and 7.22+/-0.18, respectively). There were no significant differences among the pD2 values for noradrenaline in aortic rings without endothelium. In conclusion, at high but not low doses, estradiol increased the sensitivity to noradrenaline and this was prevented by progesterone. Both of these effects were endothelium-dependent.

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.

A puzzle used to teach the cardiac cycle

The aim of the present article is to describe a puzzle developed for use in teaching cardiac physiology classes. The puzzle presents figures of phases of the cardiac cycle and a table with five columns: phases of cardiac cycle, atrial state, ventricular state, state of atrioventricular valves, and pulmonary and aortic valves. Chips are provided for use to complete the table. Students are requested to discuss which is the correct sequence of figures indicating the phases of cardiac cycle. Afterward, they should complete the table with the chips. Students of biology, dentistry, medicine, pharmacy, and nursing graduation courses from seven institutions performed the puzzle evaluation. They were invited to indicate whether the puzzle had been useful for learning about the subject by filling one of four alternatives. Of the students, 4.6% answered that it was not necessary but helped them to confirm what they had learned, 64.5% reported that although they had previously understood the cardiac cycle, the puzzle helped them to solve doubts and promoted a better understanding of it, and 30.9% said that they needed the puzzle to understand the cardiac cycle, without differences among courses, institutions, and course semesters. The results of the present study suggest that a simple and inexpensive puzzle may be useful as an active learning methodology applied after the theoretical lecture, as a complementary tool for studying cardiac cycle physiology.

Forced swim stress: supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline and the role of corticosterone.

1. Forced swim (three daily sessions) resulted in an increased plasma corticosterone level and supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline. 2. Bilateral adrenalectomy, performed 2 days before forced swim, abolished the development of pacemaker supersensitivity to isoprenaline. 3. Administration to rats of the antiglucorticoid compound RU-38486 prevented the development of pacemaker supersensitivity to isoprenaline. Pretreatment of rats not submitted to forced swim with the synthetic glucocorticoid RU-28362 causes pacemaker supersensitivity to isoprenaline. 4. Pretreatment of rats with diazepam or imipramine which block the forced swim-induced increase in the plasma level of corticosterone prevented the development of pacemaker supersensitivity to isoprenaline. 5. It is concluded that corticosterone plays a critical role in the modulation of the sensitivity to catecholamines of the pacemaker beta-adrenoceptors during adaptation to repeated stress.

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.

Relação entre a administração de esteróide anabólico androgênico, treinamento físico aeróbio e supercompensação do glicogênio

La supercompensacion de glucogeno es una de las adaptaciones inducidas por el entrenamiento fisico. Visualizando potencializar este fenomeno, muchos atletas utilizan dosis suprafisiologicas de estos esteroides anabolicos androgenicos (EAA). El objetivo de este estudio fue el de evaluar en ratas los efectos de nandrolona y del ejercicio aerobico sobre el peso corporal, los trigliceridos, la gluclosa y las reservas de glucogeno. Ratas Wistar machos fueron aleatoriamente divididas en 4 grupos: sedentarios + vehiculo (SV), entrenada + vehiculo (EV), sedentario + EAA (SEAA) y entrenada + EAA (EEAA, n = 7-14/grupo). Recibieron una inyeccion intramuscular de nandrolona en vehiculo durante dos semanas y durante este mismo periodo los animales entrenados fueron sometidos a ejercicio aerobico. Los datos fueron analizados usando las pruebas estadisticas ANOVA bifactorial y Tukey (p (SV: 0,2 ± 0,02 = SEAA: 0,21 ± 0,02mg/100mg)]. La glucemia y las reservas de glucogeno del soleo permanecieron inalteradas. El uso de dosis superfisiologicas de nandrona no potencializaron ninguno de los efectos obtenidos en respuesta al entrenamiento aerobico.Glycogen supercompensation is one of the adaptations induced by physical training. To potentiate this phenomenon, many athletes use supraphysiological doses of anabolic androgenic steroids (AAS). The purpose of this study was to evaluate the effects of nandrolo- ne and aerobic physical exercise in rats, on body weight, plasmatic triglycerides levels, blood glucose and glycogen content. Male Wistar rats were randomly divided into 4 groups: Sedentary + ve- hicle (SV), Trained + vehicle (TV), Sedentary + AAS (SAAS) and Trained + AAS (TAAS) (n = 7-14/group). They received i.m. injec- tions of nandrolone or vehicle for 9 weeks, and during the same period trained rats were submitted to aerobic exercise. Data were analyzed by two-way ANOVA and Tukey tests (p (SV: 0,2 ± 0,02 = SAAS: 0,21 ± 0,02 mg/100 mg)). Blood glucose and soleus glycogen reserves re- mained unaltered. The use of supraphysiological doses of nandrolo- ne did not potentiate any of the effects obtained in response to aerobic physical training.