Ana Cristina Silva Rebelo

Influência do uso de contraceptivos orais nos níveis lipídicos e nas respostas cardiorrespiratórias de mulheres saudáveis e sedentárias

OBJECTIVE: To evaluate the influence of oral contraceptive use on lipid levels, heart rate (HR) variability and aerobic capacity among sedentary young women. METHODS: The subjects were 20 healthy women (23.55±1.88 years): ten used oral contraceptives (TG) and ten did not (CG). Ergospirometric test on a cycle ergometer was used to determine the aerobic capacity at the anaerobic threshold and at the exercise peak. In addition, recordings of HR and R-R (iRR) intervals in the supine and seated positions, for 15 minutes, and biochemical blood analysis were performed. The iRR (ms) indices were analyzed in the time domain (TD) for RMSSD, RMSM and pNN50 (%), and in the frequency domain (FD) using fast Fourier transforms from low (LF) and high (HF) frequency bands in normalized units, obtaining the LF/HF ratio. Mann-Whitney and Kruskal-Wallis, with α=5%, were used for statistical analyses. RESULTS: The triglyceride and cholesterol levels in the TG were greater than those in the CG (p<0.05). At the anaerobic threshold and at the exercise peak, the power (W), oxygen uptake (VO2), carbon dioxide production (VCO2), (VO2/VCO2) ratio, pulmonary ventilation and HR were not significantly different between the groups. The indices for HR variability in the TD and FD for the two groups in the supine and seated positions were also not different. CONCLUSIONS: The use of oral contraceptives did not influence the aerobic capacity or the autonomic modulation of the HR. However, it influenced the total cholesterol and triglyceride levels. These assessments are important for determining protocols for physical training for cardiovascular disease prevention.

Cardiac Autonomic Modulation and the Kinetics of Heart Rate Responses in the On- and Off-Transient during Exercise in Women with Metabolic Syndrome

Objective: To test whether women with metabolic syndrome (MS) have impairments in the on- and off-transients during an incremental test and to study whether any of the MS components are independently associated with the observed responses. Research Design and Methods: Thirty-six women aged 35–55 years were divided into a group with MS (MSG, n = 19) and a control group (CG, n = 17). R-R intervals (RRi) and heart rate variability (HRV) were calculated on a beat-to-beat basis and the heart rate (HR) at the on- and off-transient were analyzed during an incremental cardiopulmonary exercise test (CPET). Results: MSG showed lower aerobic capacity and lower parasympathetic cardiac modulation at rest compared with CG. HR values in on-transient phase were significantly lower in MSG compared with CG. The exponential amplitudes “amp” and the parameters “τ” [speed of heart rate recovery (HRR)] were lower in MSG. MSG exhibited higher HR values in comparison to CG during the off-transient indicating a slower HRR. In MSG, there was an inverse and significant correlation between fasting plasma vs. ΔF and glucose vs. exponential “τ” of HRR dynamics. Conclusion: MS is associated with poor heart rate kinetics. The altered HR kinetics seems to be related to alterations in cardiac parasympathetic modulation, and glucose metabolism seems to be the major determinant.

Blockade of Rostral Ventrolateral Medulla (RVLM) Bombesin Receptor Type 1 Decreases Blood Pressure and Sympathetic Activity in Anesthetized Spontaneously Hypertensive Rats

Intrathecal injection of bombesin (BBS) promoted hypertensive and sympathoexcitatory effects in normotensive (NT) rats. However, the involvement of rostral ventrolateral medulla (RVLM) in these responses is still unclear. In the present study, we investigated: (1) the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR); (2) the contribution of RVLM BBS type 1 receptors (BB1) to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v.) were instrumented to record mean arterial pressure (MAP), diaphragm (DIA) motor, and renal sympathetic nerve activity (RSNA). In NT rats and SHR, BBS (0.3 mM) nanoinjected into RVLM increased MAP (33.9 ± 6.6 and 37.1 ± 4.5 mmHg, respectively; p < 0.05) and RSNA (97.8 ± 12.9 and 84.5 ± 18.1%, respectively; p < 0.05). In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7%; p < 0.05). BB1 receptors antagonist (BIM-23127; 3 mM) reduced MAP (–19.9 ± 4.4 mmHg; p < 0.05) and RSNA (−17.7 ± 3.8%; p < 0.05) in SHR, but not in NT rats (−2.5 ± 2.8 mmHg; −2.7 ± 5.6%, respectively). These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

Aging-Induced Biological Changes and Cardiovascular Diseases

Aging is characterized by functional decline in homeostatic regulation and vital cellular events. This process can be linked with the development of cardiovascular diseases (CVDs). In this review, we discussed aging-induced biological alterations that are associated with CVDs through the following aspects: (i) structural, biochemical, and functional modifications; (ii) autonomic nervous system (ANS) dysregulation; (iii) epigenetic alterations; and (iv) atherosclerosis and stroke development. Aging-mediated structural and biochemical modifications coupled with gradual loss of ANS regulation, vascular stiffening, and deposition of collagen and calcium often disrupt cardiovascular system homeostasis. The structural and biochemical adjustments have been consistently implicated in the progressive increase in mechanical burden and functional breakdown of the heart and vessels. In addition, cardiomyocyte loss in this process often reduces adaptive capacity and cardiovascular function. The accumulation of epigenetic changes also plays important roles in the development of CVDs. In summary, the understanding of the aging-mediated changes remains promising towards effective diagnosis, discovery of new drug targets, and development of new therapies for the treatment of CVDs.

Does the median preoptic nucleus contribute to sympathetic hyperactivity in spontaneously hypertensive rats

The present study sought to determine the involvement of median preoptic nucleus (MnPO) in the regulation of the cardiovascular function and renal sympathetic activity in normotensive (NT) and spontaneously hypertensive rats (SHR). MnPO inhibition evoked by Muscimol (4mM) nanoinjections, elicited fall in MAP and renal sympathoinhibition in NT-rats. Surprisingly, in SHRs these responses were greater than in NT-rats. These results demonstrated, for the first time that MnPO was involved in the tonic control of sympathetic activity in NT and SHRs. Furthermore, our data suggest the MnPO involvement in the increased sympathetic outflow and consequent arterial hypertension observed in SHRs.

Ação do licopeno nos músculos esquelético e cardíaco sob estresse oxidativo por exercícios

Introduction: Free radicals produced during exercise may exceed the antioxidant defense system, causing oxidative damage to specific biomolecules. The lesions caused by free radicals in cells can be prevented or reduced by natural antioxidants, which are found in many foods. Lycopene is one of the most potent carotenoids with antioxidant properties, and it is used to prevent carcinogenesis and atherogenesis, as it protects molecules such as lipids, low-density lipoproteins (LDL), proteins and DNA. Objective: To investigate the role of lycopene as a potential protector of cardiac and skeletal muscle fibers against oxidative stress during strenuous exercise, which would cause morphological changes in these tissues. Methods: The experiments consisted of 32 adult male rats divided into four groups: two control groups and two trained groups with and without lycopene supplementation (6 mg per animal). The animals of the trained groups were subjected to 42 swimming sessions over a nine-week period, involving daily swimming sessions, five days a week, with overload produced by increasing the training time. The morphological analysis was performed using histological slides of cardiac and skeletal muscle tissues. Results: Modifications were observed in cardiac and skeletal muscle tissue in the trained group that did not receive lycopene supplementation, while the trained group supplemented with lycopene showed muscle tissue with a normal morphological appearance. The tissues of both supplemented and non supplemented sedentary control groups showed no change in their histological characteristics. Conclusion: It can be stated that lycopene exerted a protective effect on cardiac and skeletal muscles against oxidative stress induced by strenuous exercise, besides promoting cardiac neovascularization, and can be used efficiently by athletes and physically active individuals.^aINTRODUCAO: Os radicais livres produzidos durante os exercicios podem exceder o sistema de defesa antioxidante, provocando danos oxidativos de biomoleculas especificas. As lesoes causadas pelos radicais livres nas celulas podem ser prevenidas ou reduzidas por meio da atividade de antioxidantes naturais, sendo estes encontrados em muitos alimentos. O licopeno e um dos mais potentes carotenoides com acao antioxidante, sendo utilizado na prevencao da carcinogenese e aterogenese por proteger moleculas como lipidios, lipoproteinas de baixa densidade (LDL), proteinas e DNA.OBJETIVO: Investigar a atuacao do licopeno a uma possivel acao protetora das fibras musculares cardiacas e esqueleticas contra o estresse oxidativo, durante a atividade fisica exaustiva, a qual provocaria alteracoes morfologicas nesses tecidos. Metodo: Na realizacao dos experimentos foram utilizados 32 ratos machos adultos divididos em quatro grupos, sendo dois grupos controles e dois grupos treinados sem e com suplementacao de licopeno (6 mg por animal). Os animais dos grupos treinados foram submetidos a 42 sessoes de natacao por nove semanas, com sessoes diarias de natacao, cinco dias por semana, com sobrecarga produzida pelo aumento do tempo de treinamento. A avaliacao morfologica foi realizada por meio de lâminas histologicas dos tecidos cardiaco e muscular esqueletico.RESULTADOS: Modificacoes teciduais cardiacas e musculares esqueleticas no grupo treinado sem suplementacao com licopeno foram observadas, sendo que o grupo treinado suplementado apresentou aspecto morfologico normal. Nos grupos sedentarios controle suplementado e nao suplementado nao houve alteracao em relacao as caracteristicas histologicas dos tecidos.CONCLUSAO: Podemos afirmar que o licopeno exerceu um efeito protetor nos musculos cardiaco e esqueletico contra o estresse oxidativo, induzido por exercicios exaustivos, alem de promover uma neovascularizacao do tecido cardiaco, podendo ser utilizado com eficiencia por atletas e praticantes de atividade fisica.^lpt^aINTRODUCTION: Free radicals produced during exercise may exceed the antioxidant defense system, causing oxidative damage to specific biomolecules. The lesions caused by free radicals in cells can be prevented or reduced by natural antioxidants, which are found in many foods. Lycopene is one of the most potent carotenoids with antioxidant properties, and it is used to prevent carcinogenesis and atherogenesis, as it protects molecules such as lipids, low-density lipoproteins (LDL), proteins and DNA.OBJECTIVE: To investigate the role of lycopene as a potential protector of cardiac and skeletal muscle fibers against oxidative stress during strenuous exercise, which would cause morphological changes in these tissues.METHODS: The experiments consisted of 32 adult male rats divided into four groups: two control groups and two trained groups with and without lycopene supplementation (6 mg per animal). The animals of the trained groups were subjected to 42 swimming sessions over a nine-week period, involving daily swimming sessions, five days a week, with overload produced by increasing the training time. The morphological analysis was performed using histological slides of cardiac and skeletal muscle tissues.RESULTS: Modifications were observed in cardiac and skeletal muscle tissue in the trained group that did not receive lycopene supplementation, while the trained group supplemented with lycopene showed muscle tissue with a normal morphological appearance. The tissues of both supplemented and non supplemented sedentary control groups showed no change in their histological characteristics.CONCLUSION: It can be stated that lycopene exerted a protective effect on cardiac and skeletal muscles against oxidative stress induced by strenuous exercise, besides promoting cardiac neovascularization, and can be used efficiently by athletes and physically active individuals.^len^aINTRODUCCION: Los radicales libres producidos durante los ejercicios pueden exceder el sistema de defensa antioxidante, provocando danos oxidativos de biomoleculas especificas. Las lesiones causadas por los radicales libres en las celulas pueden ser prevenidas o reducidas por medio de la actividad de antioxidantes naturales, siendo estos encontrados en muchos alimentos. El licopeno es uno de los mas potentes carotenoides con accion antioxidante, siendo utilizado en la prevencion de la carcinogenesis y aterogenesis por proteger moleculas como lipidos, lipoproteinas de baja densidad (LDL), proteinas y DNA.OBJETIVO: Investigar la actuacion del licopeno a una posible accion protectora de las fibras musculares cardiacas y esqueleticas contra el estres oxidativo, durante la actividad fisica exhaustiva, la cual provocaria alteraciones morfologicas en esos tejidos.METODOS: En la realizacion de los experimentos fueron utilizados 32 ratones machos adultos divididos en cuatro grupos, siendo dos grupos controles y dos grupos entrenados sin y con suplementacion de licopeno (6 mg por animal). Los animales de los grupos entrenados fueron sometidos a 42 sesiones de natacion por nueve semanas, con sesiones diarias de natacion, cinco dias por semana, con sobrecarga producida por el aumento del tiempo de entrenamiento. La evaluacion morfologica fue realizada por medio de laminas histologicas de los tejidos cardiaco y muscular esqueletico.RESULTADOS: Fueron observadas modificaciones tisulares cardiacas y musculares esqueleticas en el grupo entrenado sin suplementacion con licopeno, siendo que el grupo entrenado suplementado presento aspecto morfologico normal. En los grupos sedentarios control suplementado y no suplementado no hubo alteracion en relacion a las caracteristicas histologicas de los tejidos.CONCLUSION: Podemos afirmar que el licopeno ejercio un efecto protector en los musculos cardiaco y esqueletico contra el estres oxidativo, inducido por ejercicios exhaustivos, ademas de promover una neovascularizacion del tejido cardiaco, pudiendo ser utilizado con eficiencia por atletas y practicantes de actividad fisica.^les

Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats

The infusion of hypertonic saline solution (HSS) is known to be beneficial to the treatment of hypovolemic hemorrhage (HH). The central mechanism of HSS-induced cardiovascular and autonomic recovery of animals subjected to HH remains unclear. Hence, the present study evaluated the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats. The wistar rats were subjected to specific lesion of noradrenergic neurons through the nanoinjections of anti-DβH-saporin into caudal ventrolateral medulla (A1 neurons) and nucleus of the solitary tract (A2 neurons). After recovery, mean arterial pressure (MAP) and renal sympathetic nervous activity were recorded. The HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. In sham rats, HSS infusion (3M NaCl) reestablished MAP without change in HH-induced sympathoinhibition. The muscimol (agonist of GABAA receptor) was nanoinjected in MnPO during HH and MnPO inhibition abolished the recovery of MAP and HSS-induced sympathoinhibition. Simultaneous lesions of A1 and A2 abolished MAP restoration and sympathoinhibition after HSS infusion. These results suggest that the recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.

The Newly Synthesized Pyrazole Derivative 5-(1-(3 Fluorophenyl)-1H-Pyrazol-4-yl)-2H-Tetrazole Reduces Blood Pressure of Spontaneously Hypertensive Rats via NO/cGMO Pathway

The search for new antihypertensive drugs has grown in recent years because of high rate of morbidity among hypertensive patients and several side effects that are associated with the first-line medications. The current study sought to investigate the antihypertensive effect of a newly synthesized pyrazole derivative known as 5-(1-(3 fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-21). Spontaneously hypertensive rats (SHR) were used to evaluate the effect of LQFM-21 on mean arterial pressure (MAP), heart rate (HR), renal vascular conductance (RVC), arterial vascular conductance (AVC), baroreflex sensitivity (BRS) index, and vascular reactivity. Acute intravenous (iv) administration of LQFM-21 (0.05, 0.1, 0.2, and 0.4 mg kg-1) reduced MAP and HR, and increased RVC and AVC. Chronic oral administration of LQFM-21 (15 mg kg-1) for 15 days reduced MAP without altering BRS. The blockade of muscarinic receptors and nitric oxide synthase by intravenous infusion of atropine and L-NAME, respectively, attenuated cardiovascular effects of LQFM-21. In addition, ex vivo experiments showed that LQFM-21 induced an endothelium-dependent relaxation in isolated aortic rings from SHR. This effect was blocked by guanylyl cyclase inhibitor (ODQ) and L-NAME. These findings suggest the involvement of muscarinic receptor and NO/cGMP pathway in the antihypertensive and vasodilator effects of LQFM-21.

Associations between heart rate recovery dynamics with estradiol levels in 20 to 60 year-old sedentary women

It is hypothesized that estradiol levels, as well as aging, influence cardiac autonomic function in women. The main aim of this study was to test the correlations between heart rate recovery (HRR) dynamics, as a proxy of cardiac autonomic function, with estradiol levels and age in women. This cross-sectional study involved 44 healthy women. Heart rate (HR) data were obtained beat-by-beat during the entire experiment. Maximal incremental exercise testing (IET) on a cycle ergometer was performed followed by 6 min of recovery. During the IET recovery period, the overall HRR dynamics were evaluated by exponential data modeling (time constant “τ”) where shorter τ indicates faster HRR adjustment. Considering the cardiac autonomic complexity, HRR dynamics were also evaluated by delta (Δ) analysis considering different HR data intervals. The relationship between HRR dynamics, estradiol levels and age was tested by Pearson product-moment correlation. The overall HRR dynamics (i.e., τ) were statistically correlated with age (r = 0.58, p < 0.001) and estradiol levels (r = -0.37, p = 0.01). The Δ analysis showed that the slower overall HRR associated with aging was a consequence of slower dynamics occurring within the 45–210 s interval, indicating slower sympathetic withdrawal. In conclusion, aging effects on HRR in women seems to be correlated with a slower sympathetic withdrawal. In addition, the cardioprotective effect previously associated with estradiol seems not to influence the autonomic modulation during exercise recovery periods in women.

Antioxidant effect of the pequi oil (Caryocar brasiliense) on the hepatic tissue of rats trained by exhaustive swimming exercises

Increased oxygen consumption and activation of specific metabolic pathways during or after physical exercise lead to the formation of reactive oxygen and nitrogen species. An investigation was made into the effects of pequi oil supplementation in protecting liver cells against injury resulting from oxidative stress. The experiments involved 20 male adult Wistar rats ( Rattus norvegicus). The animals were divided into four experimental groups: Group 1: sedentary control group; Group 2: exercise control group; Group 3: supplemented sedentary group; and Group 4: supplemented exercise group. Supplementation consisted of pequi oil administered by oral gavage (400 mg). The animals of the exercised groups were subjected to 20 swimming sessions for 5 weeks (with progressive increase of 10 minutes until exhaustion). Samples were collected from the right hepatic lobe for histopathological analysis and determination of malondialdehyde levels. The histopathological analyses revealed that the animals of the exercised control group had moderate liver damage, while the animals of the supplemented exercised group had slight tissue damage, and the sedentary control and sedentary supplemented groups showed no tissue damage. The malondialdehyde levels showed higher and statistically significant in exercise control group when compared to the other evaluated groups (p<0.05). In conclusion the supplementation with pequi oil had a protective effect on liver cells against damage caused by oxygen free radicals during strenuous exercise, as demonstrated by the indicator of lipid peroxidation.