Loading...
14 results
Search Results
Now showing 1 - 10 of 14
- Essential role of RVL medullary neuronal activity in the lng term maintenance of hypertension in conscious SHRPublication . Geraldes, Vera; Gonçalves-Rosa, Nataniel; Liu, Beihui; Paton, Julian F.R.; Rocha, IsabelBackground: It is well established that sympathetic nervous system is responsible for the onset, development and maintenance of neurogenic hypertension. The rostroventrolateral medulla (RVLM) and medullo-cervical pressor area (MCPA) are important central sympathoexcitatory regions whose role on neurogenic hypertension remains unknown. Objective: To establish RVLM and MCPA roles in the long-term regulation of blood pressure by depressing their neuron activity through the over-expression of hKir2.1-potassium channel in conscious spontaneously hypertensive rats (SHR). Methods: In SHR, a lentiviral vector LVV-hKir2.1 was microinjected into RVLM or MCPA areas. A sham group was injected with LVV-eGFP. Blood pressure (BP) and heart rate (HR) were continuously monitored for 75 days. Baroreflex and chemoreflex functions were evaluated. Baroreflex gain, chemoreflex sensitivity, BP and HR variability were calculated. Results: LVV-hKir2.1 expression in RVLM, but not in MCPA, produced a significant time-dependent decrease in systolic, diastolic, mean-BP and LF of systolic BP at 60-days post-injection. No significant changes were seen in LVV-eGFP RVLM injected SHR. Conclusion: Data show that chronic expression of Kir2.1 in the RVLM of conscious SHR caused a marked and sustained decrease in BP without changes in the baro- and peripheral chemoreceptor reflex evoked responses. This decrease was mostly due to a reduction in sympathetic output revealed indirectly by a decrease in the power density of the SBP-LF band. Our data are amongst the firsts to demonstrate the role of the RVLM in maintaining BP levels in hypertension in conscious SHR. We suggest that a decrease in RVLM neuronal activity is an effective anti-hypertensive treatment strategy.
- Insights into the background of autonomic medicinePublication . Laranjo, Sergio; Geraldes, Vera; Oliveira, Mário; Rocha, IsabelKnowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction.
- Study of lead accumulation in bones of Wistar rats by X-ray fluorescence analysis: aging effectPublication . Guimarães, Diana; Carvalho, Maria Luisa; Geraldes, Vera; Rocha, Isabel; Santos, José PauloThe accumulation of lead in several bones of Wistar rats with time was determined and compared for the different types of bones. Two groups were studied: a control group (n = 20), not exposed to lead and a contaminated group (n = 30), exposed to lead from birth, first indirectly through mother's milk, and then directly through a diet containing lead acetate in drinking water (0.2%). Rats age ranged from 1 to 11 months, with approximately 1 month intervals and each of the collections had 3 contaminated rats and 2 control rats. Iliac, femur, tibia-fibula and skull have been analysed by Energy Dispersive X-ray Fluorescence Technique (EDXRF). Samples of formaldehyde used to preserve the bone tissues were also analysed by Electrothermal Atomic Absorption (ETAAS), showing that there was no significant loss of lead from the tissue to the preservative. The bones mean lead concentration of exposed rats range from 100 to 300 μg g(-1) while control rats never exceeded 10 μg g(-1). Mean bone lead concentrations were compared and the concentrations were higher in iliac, femur and tibia-fibula and after that skull. However, of all the concentrations in the different collections, only those in the skull were statistically significantly different (p < 0.05) from the other types of bones. Analysis of a radar chart also allowed us to say that these differences tend to diminish with age. The Spearman correlation test applied to mean lead concentrations showed strong and very strong positive correlations between all different types of bones. This test also showed that mean lead concentrations in bones are negatively correlated with the age of the animals. This correlation is strong in iliac and femur and very strong in tibia-fibula and skull. It was also shown that the decrease of lead accumulation with age is made by three plateaus of accumulation, which coincide, in all analysed bones, between 2nd-3rd and 9th-10th months.
- Intermittent low-level lead exposure causes anxiety and cardiorespiratory impairmentPublication . Shvachiy, Liana; Geraldes, Vera; Amaro-Leal, Ângela; Rocha, IsabelAim: To characterize behavioural and cardiorespiratory changes in a new, intermittent low-level lead exposure animal model. Introduction: Lead (Pb) is a cumulative toxic metal affecting all body systems that are particularly vulnerable during developmental phase. Permanent lead exposure has been defined as a cause of behavioural changes, cognitive impairment, sympathoexcitation, tachycardia, hypertension and autonomic dysfunction. However, no studies have been performed to describe a new, intermittent low-level lead exposure profile, that has been increased in the past years. Methods: Foetuses were intermittently (PbI) exposed to water containing lead acetate (0.2%, w/v) throughout life until adulthood (28 weeks of age). A control group (without exposure, CTL), matching in age and sex was used. At 26 weeks, behavioural tests were performed for anxiety (Elevated Plus Maze Test) and locomotor activity (Open Field Test) assessment. Blood pressure (BP), electrocardiogram (ECG), heart rate (HR) and respiratory frequency (RF) rates were recorded at 28 weeks of age. Baroreflex gain (BRG) and chemoreflex sensitivity (ChS) were calculated. Student’s T-test was used (significance p < 0.05) for statistical analysis. Results: An intermittent lead exposure causes hypertension (increased diastolic and mean BP), increased RF, decreased baroreflex function and increased ChS, without significant changes in HR, when compared to CTL group. Regarding behavioral changes, the intermittent lead exposure model showed an anxiety-like behaviour without changes in locomotor activity. Conclusion: Intermittent low-level lead exposure induces changes on the cardiorespiratory profile characterized by hypertension, carotid chemosensitivity and baroreflex impairment. According to behavioural tests results, this study also shows that the exposure to lead during developmental phases causes anxiety in adult animals without locomotor activity impairment. In summary, this study brings new insights on the environmental factors that influence nervous and cardiovascular systems during development, which can help creating public policy strategies to prevent and control the adverse effects of Pb toxicity.
- Lead in liver and kidney of exposed rats: aging accumulation studyPublication . Guimarães, Diana; Carvalho, Maria Luisa; Geraldes, Vera; Rocha, Isabel; Alves, Luís Cerqueira; Santos, José PauloThe concentration of lead in liver and kidneys of Wistar rats, fed with lead since fetal period in relation to their age and to a control group, was determined. A group of rats was exposed to lead acetate (n=30) in drinking water and the other group was exposed to normal water (n=20). Samples were collected from rats aging between 1 and 11 months and were analyzed by Energy Dispersive X-ray Fluorescence (EDXRF) without any chemical preparation. The EDXRF results were assessed by the PIXE (Proton Induced X-ray Emission) technique. The formaldehyde used to preserve the samples was also analyzed by ETAAS (Electro-Thermal Atomic Absorption Spectrometry) in order to verify if there was any loss of lead from the samples to the formaldehyde. We found that the loss was not significant (<2%). Concerning the mean values of the lead concentration measured in the contaminated soft tissues, in liver they range from 6 to 22μgg(-1), and in kidneys from 44 to 79μgg(-1). The control rats show, in general, values below the EDXRF detection limit (2μgg(-1)). The ratio kidney/liver ranges from 2 to 10 and is strongly positively correlated with the age of the animals. A Spearman correlation matrix to investigate the correlation between elemental concentrations and the dependence of these concentrations with age showed that there is a strong positive correlation with age for lead in the liver but not in the kidney. The correlation matrix showed also that the concentration of lead in these two soft tissues is not correlated. The lead accumulation in liver is made by different plateaus that strongly decrease with age. It was verified the existence of two levels of accumulation in kidney, not very highlighted, which might be indicative of a maximum accumulation level for lead in kidney.
- Acute vagal modulation of electrophysiology of the atrial and pulmonary veins increases vulnerability to atrial fibrillationPublication . Oliveira, Mario; da Silva, M. Nogueira; Geraldes, Vera; Xavier, Rita; Laranjo, Sergio; Silva, Vitor; Postolache, Gabriela; Ferreira, Rui; Rocha, IsabelVagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). We evaluated the effects of acute vagal stimulation on atrial conduction, refractoriness of atrial and pulmonary veins (PVs) and inducibility of AF. An open-chest epicardial approach was performed in New Zealand White rabbits with preserved autonomic innervation. Atrial electrograms were obtained with four unipolar electrodes placed epicardially along the atria (n = 22) and an electrode adapted to the proximal left PV (n = 10). The cervical vagus nerve was stimulated with bipolar platinum electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs), dispersion of refractoriness and conduction times from high-lateral right atrium (RA) to high-lateral left atrium (LA) and PVs assessed at baseline and during vagal stimulation. Burst pacing (50 Hz, 10 s), alone or combined with vagal stimulation, was applied to the right (RAA) and left atrial appendage (LAA) and PVs to induce AF. At baseline, ERPs were lower in PVs than in LA and LAA, but did not differ significantly from RA and RAA, and there was a significant delay in the conduction time from RA to PVs compared with the activation time from RA to LA (P < 0.01). During vagal stimulation, ERP decreased significantly at all sites, without significant differences in the dispersion of refractoriness, and the atrial conduction times changed from 39 ± 19 to 49 ± 9 ms (RA to PVs; n.s.) and from 14 ± 7 to 28 ± 12 ms (RA to LA; P = 0.01). Induction of AF was reproducible in 50% of cases with 50 Hz and in 82% with 50 Hz combined with vagal stimulation (P < 0.05). During vagal stimulation, AF cycle length decreased at all sites, and AF duration changed from 1.0 ± 0.9 to 14.0 ± 10.0 s (P < 0.01), with documentation of PV tachycardia in three cases. In 70% of the animals, AF ceased immediately after interruption of vagal stimulation. We conclude that in the intact rabbit heart, vagal activity prolongs interatrial conduction and shortens atrial and PV ERP, contributing to the vulnerability to the induction and maintenance of AF. This model may be useful in the assessment of the autonomic influence in the mechanisms underlying AF.
- Intermittent low-level lead exposure provokes anxiety, hypertension, autonomic dyfunction and neuroinflammationPublication . Shvachiy, Liana; Geraldes, Vera; Leal, Ângela Amaro; Rocha, IsabelBackground: Exposures to lead (Pb) during developmental phases can alter the normal course of development, with lifelong health consequences. Permanent Pb exposure leads to behavioral changes, cognitive impairment, sympathoexcitation, tachycardia, hypertension and autonomic dysfunction. However, the effects of an intermittent lead exposure are not yet studied. This pattern of exposure has been recently increasing due to migrations, implementation of school exchange programs and/or residential changes. Objective: To determine and compare lead effects on mammal’s behavior and physiology, using a rat model of intermittent and permanent Pb exposures. Methods: Fetuses were intermittently (PbI) or permanently (PbP) exposed to water containing lead acetate (0.2% w/v) throughout life until adulthood (28 weeks of age). A control group (CTL) without any exposure to lead was also used. Anxiety was assessed by elevated plus maze (EPM) and locomotor activity and exploration by open field test (OFT). Blood pressure (BP), electrocardiogram (ECG), heart rate (HR), respiratory frequency (RF), sympathetic and parasympathetic activity and baro- and chemoreceptor reflex profiles were evaluated. Immunohistochemistry protocol for the assessment of neuroinflammation, neuronal loss (NeuN), gliosis and synaptic alterations (Iba-1, GFAP, Syn), were performed at the hippocampus. One-way ANOVA with Tukey’s multiple comparison between means were used (significance p < 0.05) for statistical analysis. Results: The intermittent lead exposure produced a significant increase in diastolic and mean BP values, concomitant with a tendency to sympathetic overactivity (estimated by increased low-frequency power) and without significant changes in systolic BP, HR and RF. A chemoreceptor hypersensitivity and a baroreflex impairment were also observed, however, less pronounced when compared to the permanent exposure. Regarding behavioral changes, both lead exposure profiles showed an anxiety-like behavior without changes in locomotor and exploratory activity. Increase in GFAP and Iba-1 positive cells, without changes in NeuN positive cells were found in both exposed groups. Syn staining suffered a significant decrease in PbI group and a significant increase in PbP group. Conclusion: This study is the first to show that developmental Pb exposure since fetal period can cause lasting impairments in physiological parameters. The intermittent lead exposure causes adverse health effects, i.e, hypertension, increased respiratory frequency and chemoreflex sensitivity, baroreflex impairment, anxiety, decreased synaptic activity, neuroinflammation and reactive gliosis, in some ways similar to a permanent exposure, however some are lower-grade, due to the shorter duration of exposure. This study brings new insights on the environmental factors that influence autonomic and cardiovascular systems during development, which can help in creating public policy strategies to prevent and control the adverse effects of Pb toxicity.
- Hypothalamic and medullar mechanisms for long-term autonomic regulation of arterial blood pressurePublication . Geraldes, Vera; Rocha, Isabel, 1964-; Outeiro, Tiago Fleming, 1976-
- Hypothalamic Ion channels in hypertensionPublication . Geraldes, Vera; Laranjo, Sergio; Rocha, IsabelHypertension is a prevalent and major health problem, involving a complex integration of different organ systems, including the central nervous system (CNS). The CNS and the hypothalamus in particular are intricately involved in the pathogenesis of hypertension. In fact, evidence supports altered hypothalamic neuronal activity as a major factor contributing to increased sympathetic drive and increased blood pressure. Several mechanisms have been proposed to contribute to hypothalamic-driven sympathetic activity, including altered ion channel function. Ion channels are critical regulators of neuronal excitability and synaptic function in the brain and, thus, important for blood pressure homeostasis regulation. These include sodium channels, voltage-gated calcium channels, and potassium channels being some of them already identified in hypothalamic neurons. This brief review summarizes the hypothalamic ion channels that may be involved in hypertension, highlighting recent findings that suggest that hypothalamic ion channel modulation can affect the central control of blood pressure and, therefore, suggesting future development of interventional strategies designed to treat hypertension.
- Autonomic function evaluation in an intermittent lead exposure animal modelPublication . Shvachiy, Liana; Geraldes, Vera; Carvalho, Mafalda; Rocha, IsabelLead (Pb) is a toxic metal, which widespread use has resulted in environmental contamination, human exposure and significant public health problems. The autonomic nervous system, being a homeostatic controller, is impaired in acute and chronic lead exposure. In fact, sympathoexcitation associated to hypertension and tachypnea has been described together with baroreflex and chemoreflex dysfunction. However, up to date, no studies described the autonomic effects of an intermittent low-level lead exposure. In the present work, we addressed in vivo, autonomic behaviour in rats under chronic Pb exposure (control) and in rats under intermittent Pb exposure. For that, arterial blood pressure (BP) and ECG were recorded in 28 weeks old animal and low frequencies (LF) and high frequencies (HF) were determined (to estimate sympathetic and parasympathetic activities) using FisioSinal software with Wavelet module. Preliminary results: Rats intermittently exposed to lead showed a significant decrease in systolic BP (126 ± 4 vs 144 ± 3 mmHg) with no significant changes in LF, HF and LF/HF bands (1.5 ± 0.3 vs 1.7 ± 0.5 mmHg2, 1.9 ± 0.7 vs 2.8 ± 1.2 bpm2 and 1.2 ± 0.4 vs 1.1 ± 0.3 mmHg2/bpm2, respectively) when compared to chronically Pb exposed rats. Our data suggests that the autonomic dysfunction induced by lead exposure is similar in a chronic and intermittent Pb exposure. Nevertheless, it seems that an intermittent exposure was no effect on systolic BP values. The present study brings new insights on the environmental factors that influence autonomic and cardiovascular systems during development, which can help apprise public policy strategies to prevent and control the adverse effects of Pb toxicity.