Thesis (Ph. D.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains xii, 195 p. : ill. Vita. Includes abstract. Includes bibliographical references.

A. INTRODUCTION<p>A.1. The sympathetic nervous system.<p>A.1.1. General considerations and historical perspective.<p>A.1.1.1. Historical perspective<p>A.1.1.2. Reflex regulation of the autonomic nervous system<p>A.1.1.3. Central control of the autonomic nervous system<p>A.1.1.4. Sympathetic and parasympathetic components of the autonomic<p>nervous system<p>A.1.1.5. Organisation of the sympathetic nervous system<p>A.1.1.6. Functions of the sympathetic nervous system<p>A.1.1.7. Neurotransmitters of the sympathetic nervous system<p>A.1.1.8. Neurotransmitter secretion at effectors organ synapse<p>A.1.1.9. Adrenoreceptors<p>A.1.2. Control mechanisms<p>A.1.2.1. Aortic arch and carotid baroreceptors<p>A.1.2.2. Low pressure baroreceptors<p>A.1.2.3. Chemoreceptors<p>A.1.2.4. Effects of exercise on sympathetic nervous system activation<p>A.1.2.5. Effects of left ventricular dysfunction on sympathetic nervous<p>system activation<p>A.1.2.6. Effects of right ventricular dysfunction and heart<p>transplantation on sympathetic nervous system activity<p>A.2. Methodological considerations.<p>A.2.1. Assessment of sympathetic activity in humans<p>A.2.2. Circulating catecholamines<p>A.2.3. Microneurography<p>A.3. Ergospirometry<p>A.3.1. Several aspects of physiology of exercise<p>A.3.2. Principles of exercise testing<p>A.3.3. Exercise ventilation<p>A.4. Assessment of chemoreceptor regulation in humans<p>A.4.1. Peripheral chemoreceptor inhibition<p>A.4.2. Peripheral and central chemoreceptor activation<p>A.5. Brief summary of still unresolved questions<p>A.5.1. Pulmonary arterial hypertension<p>A.5.2. Heart transplantation<p>B. SYMPATHETIC CONTROL IN PULMONARY ARTERIAL HYPERTENSION<p>B.1. Hypothesis tested<p>B.2. Study populations<p>B.2.1. Study investigating sympathetic activity in PAH patients<p>B.2.2. Study investigating the effects of atrial septostomy on MSNA in PAH<p>patients<p>B.3. Material, methods and study protocols<p>B.3.1. Particular measurements in the study investigating sympathetic activity<p>in PAH patients<p>B.3.2. Particular measurements in the study investigating effects of atrial<p>septostomy on MSNA in PAH patients<p>B.4. Sympathetic nervous activity in PAH and effects of disease severity<p>B.5. Effects of chemoreflex activation<p>B.6. Effects of atrial septostomy<p>C. SYMPATHETIC CONTROL AFTER HEART TRANSPLANTATION<p>C.1. Hypothesis tested<p>C.2. Patient population<p>C.3. Material and methods<p>C.4. Effects of chemoreflex activation on sympathetic activity and blood pressure<p>C.5. Effects of chemoreflex activation on exercise intolerance<p>D. DISCUSSION<p>D.1. Sympathetic nervous system activation in patients with pulmonary arterial<p>hypertension<p>D.2. Effects of atrial septostomy on sympathetic nervous system activation<p>D.3. Chemoreceptors in heart transplant recipients<p>D.3.1. Peripheral chemoreceptors deactivation<p>D.3.2. Peripheral and central chemoreceptors sensitivity<p>E. CONCLUSIONS<p>F. REFERENCE LIST<p>G. ANNEXES<p>G.1. Publications<p>G.1.1. Velez-Roa and Ciarka et al, Increased sympathetic nerve activity in<p>pulmonary artery hypertension, Circulation. 2004 Sep 7;110(10):1308-<p>12.<p>G.1.2. Ciarka et al, Atrial septostomy decreases sympathetic overactivity in<p>pulmonary arterial hypertension, Chest. 2007 Jun;131(6):1831-7.<p>G.1.3. Ciarka et al, Effects of peripheral chemoreceptors deactivation on<p>sympathetic activity in heart transplant recipients. Hypertension. 2005<p>May;45(5):894-900.<p>G.1.4. Ciarka et al, Increased peripheral chemoreceptors sensitivity and<p>exercise ventilation in heart transplant recipients. Circulation. 2006 Jan<p>17;113(2):252-7.<p>G.2. Annexe thesis title.<p>G.3. Brief summary in French of described research / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Motivation The prevalence of cardiovascular disease is on the increase in sub-Saharan Africa largely owing to lifestyle changes associated with urbanisation. Traditional diets are being replaced with diets high in saturated fat and sugar. In addition to the nutritional transition, urbanisation in developing African countries also contributes to a more sedentary lifestyle. Together these trends contribute to a higher prevalence of obesity and hypertension that are major risk factors for the development of cardiovascular disease. Adipose tissue is now widely recognised as an endocrine organ that secretes numerous inflammatory mediators as well as adipocytokines such as leptin. The primary role of leptin is to induce satiety after a meal and to suppress appetite. However, in recent years the role of leptin in the development of obesity-related cardiovascular disease has gained increasing attention and interest. Furthermore, leptin levels not only differ with regard to gender but also ethnicity. Africans have higher leptin levels than Caucasians due to higher subcutaneous fat in Africans. Furthermore, the prevalence of hypertension and stroke are also greater in the African population. Taken together, it is important to investigate mechanisms by which elevated leptin may contribute to the development of cardiovascular disease, especially in cardiovascular disease-prone Africans. Aim The general aim of this study is to increase our understanding of the role of leptin in cardiovascular disease development by investigating associations of leptin with markers of sympathetic activity, endothelial dysfunction, and cardiovascular reactivity and recovery in Africans and Caucasians. Methodology Data from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was used and presented in the original research articles described in Chapter 2, 3 and 4. This study included 409 African and Caucasian schoolteachers working in the Potchefstroom district in the North West Province of South Africa. Groups were stratified by ethnicity, gender and ethnicity or obesity in order to demonstrate potential differences. We performed cardiovascular measurements and determined levels of leptin, renin, cortisol, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) and urinary albumin-to-creatinine ratio (ACR). Independent t-tests were done to compare means between groups and Chi-square tests to compare proportions. Pearson’s correlations were determined to investigate associations as well as partial correlations after minimal adjustment for potential confounders. Multiple regression analyses were performed to investigate independent associations of leptin with cardiovascular and biochemical markers according to the specific focus of each research manuscript. Results and conclusions of the individual manuscripts  Leptin may contribute to obesity-related hypertension through its sympatho-activating effects. In the first research article (Chapter 2), we compared mean leptin levels and markers of autonomic activity between Africans and Caucasians. We also investigated associations between markers of autonomic activity and leptin. Africans had higher leptin, body mass index, blood pressure and heart rate compared to Caucasians. Furthermore, Africans also demonstrated reduced heart rate variability that is indicative of autonomic imbalance. Markers of autonomic activity that collectively reflected sympathetic overactivity associated with leptin in both Africans and Caucasians, independent of significant covariates and confounders including body mass index. These findings suggest that leptin may contribute to the development of hypertension by inducing autonomic dysfunction.  Leptin exerts direct vascular effects and may thereby contribute to increased cardiovascular disease risk in the obese. We therefore investigated associations between circulating markers of endothelial dysfunction (PAI-1, vWF and ACR) and leptin in lean and obese groups, irrespective of ethnicity (Chapter 3). As expected, leptin and plasminogen activator inhibitor-1 antigen levels were higher in the obese group. We found no differences for von Willebrand factor antigen and urinary albumin-to-creatinine ratio. In the obese group, all markers of endothelial dysfunction were positively associated with leptin in univariate analysis. However, after full adjustment in multiple regression analyses, only the association with plasminogen activator inhibitor-1 remained significant. Higher leptin levels in the obese may possibly induce endothelial dysfunction through mechanisms related to thrombotic vascular disease.  Greater cardiovascular reactivity to stress and prolonged recovery thereafter associates with increased cardiovascular disease risk. In the final research article (Chapter 4), we therefore investigated the relationship between cardiovascular reactivity and recovery to acute stress, induced by the cold pressor test, and leptin in Africans and Caucasians. Africans demonstrated greater cardiovascular reactivity compared to Caucasians. Associations of blood pressure, stroke volume, cardiac output, total peripheral resistance and arterial compliance reactivity with leptin were investigated during the stressor application and 1, 3 and 5 minutes post-stressor. There were no independent associations between cardiovascular reactivity and leptin during the stressor, and a few correlations at 1 and 3 minutes post-stressor. Associations were mostly evident at 5 minutes post-stressor and in Africans. We argue that higher leptin levels relate to impaired post-stress recovery and thereby could contribute to hypertension development in Africans. General conclusion Elevated leptin relates to sympathetic overactivity, vascular damage and delayed post-stress recovery, and thereby could contribute to increased cardiovascular disease risk. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Motivation The prevalence of cardiovascular disease is on the increase in sub-Saharan Africa largely owing to lifestyle changes associated with urbanisation. Traditional diets are being replaced with diets high in saturated fat and sugar. In addition to the nutritional transition, urbanisation in developing African countries also contributes to a more sedentary lifestyle. Together these trends contribute to a higher prevalence of obesity and hypertension that are major risk factors for the development of cardiovascular disease. Adipose tissue is now widely recognised as an endocrine organ that secretes numerous inflammatory mediators as well as adipocytokines such as leptin. The primary role of leptin is to induce satiety after a meal and to suppress appetite. However, in recent years the role of leptin in the development of obesity-related cardiovascular disease has gained increasing attention and interest. Furthermore, leptin levels not only differ with regard to gender but also ethnicity. Africans have higher leptin levels than Caucasians due to higher subcutaneous fat in Africans. Furthermore, the prevalence of hypertension and stroke are also greater in the African population. Taken together, it is important to investigate mechanisms by which elevated leptin may contribute to the development of cardiovascular disease, especially in cardiovascular disease-prone Africans. Aim The general aim of this study is to increase our understanding of the role of leptin in cardiovascular disease development by investigating associations of leptin with markers of sympathetic activity, endothelial dysfunction, and cardiovascular reactivity and recovery in Africans and Caucasians. Methodology Data from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was used and presented in the original research articles described in Chapter 2, 3 and 4. This study included 409 African and Caucasian schoolteachers working in the Potchefstroom district in the North West Province of South Africa. Groups were stratified by ethnicity, gender and ethnicity or obesity in order to demonstrate potential differences. We performed cardiovascular measurements and determined levels of leptin, renin, cortisol, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) and urinary albumin-to-creatinine ratio (ACR). Independent t-tests were done to compare means between groups and Chi-square tests to compare proportions. Pearson’s correlations were determined to investigate associations as well as partial correlations after minimal adjustment for potential confounders. Multiple regression analyses were performed to investigate independent associations of leptin with cardiovascular and biochemical markers according to the specific focus of each research manuscript. Results and conclusions of the individual manuscripts  Leptin may contribute to obesity-related hypertension through its sympatho-activating effects. In the first research article (Chapter 2), we compared mean leptin levels and markers of autonomic activity between Africans and Caucasians. We also investigated associations between markers of autonomic activity and leptin. Africans had higher leptin, body mass index, blood pressure and heart rate compared to Caucasians. Furthermore, Africans also demonstrated reduced heart rate variability that is indicative of autonomic imbalance. Markers of autonomic activity that collectively reflected sympathetic overactivity associated with leptin in both Africans and Caucasians, independent of significant covariates and confounders including body mass index. These findings suggest that leptin may contribute to the development of hypertension by inducing autonomic dysfunction.  Leptin exerts direct vascular effects and may thereby contribute to increased cardiovascular disease risk in the obese. We therefore investigated associations between circulating markers of endothelial dysfunction (PAI-1, vWF and ACR) and leptin in lean and obese groups, irrespective of ethnicity (Chapter 3). As expected, leptin and plasminogen activator inhibitor-1 antigen levels were higher in the obese group. We found no differences for von Willebrand factor antigen and urinary albumin-to-creatinine ratio. In the obese group, all markers of endothelial dysfunction were positively associated with leptin in univariate analysis. However, after full adjustment in multiple regression analyses, only the association with plasminogen activator inhibitor-1 remained significant. Higher leptin levels in the obese may possibly induce endothelial dysfunction through mechanisms related to thrombotic vascular disease.  Greater cardiovascular reactivity to stress and prolonged recovery thereafter associates with increased cardiovascular disease risk. In the final research article (Chapter 4), we therefore investigated the relationship between cardiovascular reactivity and recovery to acute stress, induced by the cold pressor test, and leptin in Africans and Caucasians. Africans demonstrated greater cardiovascular reactivity compared to Caucasians. Associations of blood pressure, stroke volume, cardiac output, total peripheral resistance and arterial compliance reactivity with leptin were investigated during the stressor application and 1, 3 and 5 minutes post-stressor. There were no independent associations between cardiovascular reactivity and leptin during the stressor, and a few correlations at 1 and 3 minutes post-stressor. Associations were mostly evident at 5 minutes post-stressor and in Africans. We argue that higher leptin levels relate to impaired post-stress recovery and thereby could contribute to hypertension development in Africans. General conclusion Elevated leptin relates to sympathetic overactivity, vascular damage and delayed post-stress recovery, and thereby could contribute to increased cardiovascular disease risk. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Hypertension affects 1 in 3 adults and is the single greatest risk factor for premature death. Salt-sensitive hypertension occurs in approximately 50% of hypertensive patients and results in a 3-fold increase in the risk of adverse cardiovascular events. However, the pathophysiology of salt-sensitive hypertension remains to be fully elucidated. There has been increased interest in the interaction between the sympathetic nervous system and the kidney and how that interaction mediates sodium excretion to drive the development of salt-sensitivity. Previous studies show that sympathetic over-activity increases expression of the sodium chloride cotransporter (NCC) resulting in increased NCC-mediated sodium reabsorption, and the development of salt-sensitive hypertension. In this thesis, I show the effect of increased norepinephrine (NE) and high salt intake in salt-resistant vs. salt-sensitive rat phenotypes on blood pressure regulation, NCC activity, and the adrenoreceptor-mediated regulatory kinase network signal transduction pathway. A high salt diet 1) exacerbates NE-induced hypertension in salt-resistant Sprague-Dawley (SD) rats and 2) results in hypertension in Dahl salt-sensitive (DSS) rats. In contrast to salt-resistant phenotypes (SD & Dahl salt-resistant), dietary sodium-evoked suppression of NCC expression and activity is prevented in salt-sensitive rats (SD-NE infusion & DSS) - I show that this occurs through a failure of a high salt intake to suppress renal OxSR1, SPAK, and WNK1 (NCC regulatory proteins). I demonstrate that α1-adrenoreceptors are responsible for mediating the salt-sensitive component of hypertension and restore dietary sodium-evoked suppression of the NCC via a predominant OxSR1 pathway. Chronic β-adrenoreceptor antagonism significantly reduces blood pressure in NE-mediated hypertension. How the body senses salt remains unknown, but my data show that selective removal of the afferent renal nerves prevents dietary sodium-evoked suppression of NCC expression and activity resulting in salt-sensitive hypertension, suggesting that the afferent renal nerves play an important role as a sodium-sensing mechanism. Overall, these data demonstrate that attenuated afferent renal nerve feedback drives renal efferent nerve release of NE to prevent the downregulation of the NCC via an α1-adrenergic receptor-gated WNK1-OxSR1 signal transduction pathway to evoke the development of salt-sensitive hypertension.

Dados recentes mostram que o remodelamento ósseo está sujeito ao controle do SNC, com o SNS. Para tanto, avaliamos o (CLO) e a morfologia da (LE) do fêmur de camundongos de 21 dias de idade selvagens (WT) e Knockout (KO) para a2CAR, tratados, para mimetizar o hipertiroidismo (Hiper) ou tratados para indução do hipotiroidismo (Hipo). Os animais KO eutiroideos (Eut) apresentaram uma desorganização da ZP e aumento do número de CHM da LE. Nos animais WT, o Hipo promoveu redução do CLO, desorganização da ZP e diminuição do número de CHM. O Hipo promoveu efeitos contrários na LE dos animais KO em relação aos animais WT, sendo capaz de reverter, parcialmente, a desorganização da ZP dos camundongos KO Eut, além de resultar em maior número de CHM, em relação aos animais WT Hipo. Já o Hiper levou a aumento do número de CH nos animais WT e redução nos animais KO. Os animais KO Hiper apresentaram diminuição de CHM, quando comparados aos animais WT Hiper. Esses achados reforçam as hipóteses de que o SNS regula o CLO via a2CAR e que o HT e SNS interagem para regular o CLO. / Recent data show that bone remodeling is under control of the CNS, with the SNS. Thus, we evaluated the bone growth and the morphology of the femoral EGP of 21- day old female wild-type (WT) and a2CAR-/- mice (KO), treated to mimic hyperthyroidism (Hyper), or treated for hypothyroidism (Hypo). The euthyroid KO mice had a disorganization of PZ and increase in the number of MHC of the EGP. In WT animals, Hypo promoted a significant reduction in the BLG, PZ disorganization and a decreased number of MHC. Hypo promoted opposite effects in EGP of KO compared to WT mice. Hypo was able to partially revert the PZ disorganization observed in euthyroid KO, and resulted in a greater number of MHC compared to WT Hypo. On the other hand, Hyper caused an increase in the number of HC in WT mice and a reduction in KO mice. Furthermore, Hyper KO animals showed a reduction in the number of MHC, when compared to the Hyper WT mice. These findings support the hypothesis that the SNS regulates the BLG via a2CAR and that the interaction between SNS and TH can regulate the BLG.

Sabe-se que o hormônio tireoideano (HT) é essencial para o crescimento e desenvolvimento ósseos. No entanto, os mecanismos pelos quais o HT regula esses processos são pouco entendidos. Recentemente, o sistema nervoso simpático (SNS) foi identificado como um potente regulador do metabolismo ósseo. Estudos do nosso grupo mostraram que o HT interage com o SNS para regular a massa e estrutura ósseas, e que essa interação envolve a sinalização adrenoceptora &#945;2 (&#945;2-AR). Também identificamos a presença de todos os subtipos de adrenoceptores &#945;2 adrenérgicos, o &#945;2A- , &#945;2B- e &#945;2C-AR, na lâmina epifiseal (LE) de camundongos. Além disso, observamos que camundongos com inativação gênica isolada do &#945;2A-AR e &#945;2C-AR (&#945;2A-AR -/- e &#945;2C-AR -/- ) apresentam LEs desorganizadas, ossos longos mais curtos, e atraso na ossificação endocondral. Estudos in vivo revelaram, que as LEs de animais &#945;2A-AR -/- e &#945;2C-AR -/- respondem de forma diferente (do que as LEs de animais selvagens) ao excesso e deficiência de HT, o que sugere fortemente que o HT também interage com o SNS para regular o crescimento e o desenvolvimento ósseos. Através de um sistema de cultura de órgãos de ossos longos, o presente estudo teve como objetivo investigar se o HT interage com o SNS diretamente no esqueleto, para regular o crescimento linear ósseo, e se os receptores &#945;2 adrenérgicos estão envolvidos nessa interação. Assim sendo, avaliamos, in vitro, o crescimento linear ósseo de tíbias derivadas de embriões de camundongos (com 15 dias de vida intrauterina) selvagens (WT) e &#945;2C- AR -/- (KO) durante 6 dias. Vimos que as tíbias KO apresentam um menor crescimento longitudinal quando comparadas às tíbias WT, e que o tratamento com 10-8 M de triiodotironina (T3) diminuiu significativamente o crescimento longitudinal das tíbias WT, o que não foi visto nas tíbias KO. Vimos, ainda, que o tratamento com UK 14,304 (UK), um agonista &#945;2 não seletivo, induziu o crescimento longitudinal somente nas tíbias KO. A expressão de genes relacionados com a diferenciação terminal de condrócitos (Col X, IGF-1, Wnt-4 e Runx2) mostrou-se aumentada nas tíbias KO (quando comparada à expressão nas tíbias WT). O tratamento com T3, como esperado, estimulou a expressão desses genes nas tíbias WT, porém diminui a expressão nas amostras KO, chamando a atenção para a importância desses receptores na modulação das ações do T3. Observamos, ainda, que a ativação local dos &#945;2- ARs com o UK bloqueia a expressão desses genes relacionados à diferenciação dos condrócitos, além de bloquear os efeitos positivos do T3 (UK+T3) na expressão desses genes. Esses achados mostram que os receptores &#945;2 adrenérgicos atuam diretamente no esqueleto para controlar a diferenciação terminal dos condrócitos e, portanto, o crescimento longitudinal ósseo, além de permitirem uma interação com a via de sinalização do HT para controlar esses processos. Em conclusão, este estudo mostra que HT interage com o SNS, localmente no esqueleto, via sinalização &#945;2 adrenérgica, para modular o crescimento linear ósseo. / It is well known that thyroid hormone (TH) is essential for normal bone growth and development. However, the mechanisms by which TH regulates these processes are poorly understood. Recently, the sympathetic nervous system (SNS) was identified as a potent regulator of bone metabolism. In vivo studies by our group have shown that TH interacts with the SNS to regulate bone mass and structure, and that this interaction involves &#945;2 adrenoceptor (&#945;2-AR) signaling. We have also identified the presence of &#945;2A- , &#945;2B- e &#945;2C-AR subtypes in the epiphyseal growth plate (EGP) of mice. In addition, we have found that mice with isolated gene deletion of &#945;2A-AR and &#945;2C-AR (&#945;2A-AR -/- and &#945;2C- AR -/- ) show a disorganized EGP, shorter long bones and a delay in endochondral ossification (EO). In vivo studies revealed that the EGP of &#945;2A-AR -/- and &#945;2C-AR -/- animals respond differently (than those of wild-type animals), to TH excess and deficiency, which strongly suggests that TH also interacts with the SNS to regulate bone growth and development. Through a long bone organ culture system, the present study had the goal of investigating if TH interacts with the SNS directly in the skeleton, to regulate the longitudinal bone growth and if &#945;2-AR is involved in this process. Therefore, we evaluated the linear bone growth of tibias derived from 15.5-day-old WT and &#945;2C-AR -/- mouse embryos (E15.5) for 6 days. We have seen that the KO tibias showed a lower longitudinal growth when compared to WT tibias, and that treatment with 10-8 M triiodothyronine (T3) significantly decreased the longitudinal growth of the WT tibias, which was not seen in the KO tibias. We found that the treatment with UK 14.304 (UK), a non-selective &#945;2-agonist, induced the longitudinal growth only of the KO tibias. The expression of genes related to the terminal differentiation of chondrocytes (Col X, IGF-1, Wnt-4 and Runx2) was shown to be increased in the KO tibias (when compared to the expression in WT tibias). Treatment with T3, as expected, stimulated the expression of these genes in WT tibias, but decreased the expression in KO samples, highlighting the importance of these receptors in the modulation of T3 actions. We observed that the local ? 2 -AR activation by UK blocked the expression of these chondrocyte differentiation- related genes, in addition to blocking the positive effects of T3 (UK + T3) in the expression of these genes. These findings show that &#945;2 adrenoceptors act directly in the skeleton, to control the terminal differentiation of chondrocytes and, therefore, the longitudinal bone growth, in addition to allow an interaction with the TH signaling pathway to control these processes. In conclusion, this study shows that TH interacts with the SNS, locally in the skeleton, via &#945;2 adrenergic signaling, to modulate the longitudinal bone growth.

A presença de receptores de estrogênio no coração, músculo liso vascular e em centros cerebrais sugere a influência desse hormônio na regulação cardiovascular tanto durante o repouso quanto durante o estresse físico. O ojetivo desse estudo foi comparar as respostas hemodinâmicas e neurais ao exercício físico em 10 mulheres jovens (J) e em 10 mulheres pós-menopausa (PM). Métodos: A pressão arterial sistólica (PAS), média (PAM) e diastólica (PAD) foram analisadas pelo método oscilométrico (Dixtal), a freqüência cardíaca (FC) pelo ECG, a atividade nervosa simpática periférica (ANSP) pela microneurografia, pré, durante e pós-exercícios estáticos (E) e dinâmicos (D) a 10% e a 30% da contração voluntária máxima. Pós-exercícios a 30%, a circulação no antebraço foi ocluída (Ov) por 2 min. O fluxo sangüíneo no antebraço (FSA) foi mensurado pela pletismografia de oclusão venosa a ar e a resistência vascular periférica a partir da relação FSA / PAM. Os dados coletados durante o período de repouso, bem como os dados da Monitorização Ambulatorial da Pressão Arterial (MAPA) foram analisados através do teste t Studen. Os dados da sessão experimental (? e ?%; expressos em média mais ou menos erro padrão) foram comparados pela análise de variância ANOVA de dois caminhos para amostras dependentes sendo aceito como significante P<= 0,05. Resultados: Durante o período de repouso, as mulheres J apresentaram ANSP, PAS, PAM e PAD (registrados na perna) significantemente menores do que o grupo PM. O FSA apresentou maiores valores nas J quando comparadas às PM. Além disso, a RVP parece estar aumentada em PM, no entanto, os valores verificados não foram estatisticamente significantes. Durante o exercício J apresentaram variações relativas de ANSP significativamente maiores em resposta ao exercício E 10% e a 30% da CVM a qual é mantida durante a Ov e em resposta ao exercício D10% da CVM. As mulheres PM apresentaram variações relativas de FC significativamente maiores em resposta aos exercícios E 30% e D 30% que não se mantêm durante a Ov. Não houve diferença significante na MAPA durante o período de vigília, no entanto, durante o período de sono, os valores de PAD foram menores em J. A queda noturna foi significantemente maior em J do que em PM. Conclusões: O presente estudo demonstrou uma possível relação entre a atenuação da sensibilidade quimiorreflexa e o aumento do controle do comando central na população PM em resposta o exercício físico que pode estar relacionado ao estrogênio por si só ou à associação entre deficiência estrogênica e envelhecimento / The presence of estrogen receptors in the heart, vascular smooth muscle, autonomic brain centers suggest it\'s possible involvement in the regulation of cardiovascular system during and during physical stress.Objective: The aim of this study was to compare haemodynamic and neural responses to physical exercise in 10 young women (Y) and 10 women post menopause (PM).Methods: Systolic Blood Pressure (SBP), Mean Blood Pressure (MBP) and Diastolic Blood Pressure (DBP) were registered by the oscilometric method (Dixtal), heart rate (HR) by ECG, muscle sympathetic nerve activity (MSNA) was accessed by microneurography, before, during and after static (S) and dynamic (D) exercise at 10% and 30% of maximal voluntary contraction (MVC). Post exercise flow ischemia (PEI) was performed for 2 minutes after the exercise at 30% MVC. Muscle blood flow (MBF) was registered by venous occlusion pletismography. Vascular resistance (VR) was calculated by MBP/MBF. The data form 24h Ambulatory Blood Pressure (ABP) and rest period were compared by the t Student test. During exercise MSNA, SBP, DBP, MBP, HR (? and ?%; mean ± standard error) data were analyzed by using two-way within-subject factors repeated-measures ANOVA, values of p<=0.05 were considered to be statistically significant. Results: During the rest period, Y had MSNA, SBP,MBP and DBP (registered in the leg) significantly lower than PM. MBF was superior in Y when compared to PM. Besides that, VR seems to be greater in PM than in Y, even though these values were not statistically significant. During exercise, Y had relative variations of MSNA significantly grater than PM during S 10% and S 30% MVC exercise which is maintained during PEI, and at D 10% MVC exercise. PM women had relative variations of HR significantly grater than Y during exercise at 30% (static and dynamic) which was not maintained at PEI. There were no significant differences at 24h ABP during day time registers, but during night time, DBP is significantly lower in the Y. Night time fall was bigger in the Y when compared to PM. Conclusion: The present study showed a possible relation between the attenuation of chemioreflex sensibility and the increase in the central command control in the PM during exercise. This response might be associated to lack of estrogen its self or to the association of estrogen deficiency and aging

Evidências sugerem que o carvedilol diminui a atividade nervosa simpática muscular (ANSM) nos pacientes com insuficiência cardíaca (IC), mas não melhora o fluxo sangüíneo muscular (FSM) e a capacidade funcional nestes pacientes. Por outro lado, o treinamento físico reduz a ANSM, além de melhorar o FSM e a capacidade funcional nos pacientes com disfunção ventricular que não utilizam -bloqueadores. O objetivo deste estudo foi investigar o efeito do treinamento físico sobre a ANSM, FSM e capacidade funcional em pacientes com IC em uso de carvedilol. Foram estudados vinte e sete pacientes com IC, tratados com carvedilol, CF II-III, FE<35%, VO2 pico <20 ml/Kg/ min. Os pacientes foram randomizados em dois grupos: treinamento físico (n-15) e não treinamento (n-12). A ANSM foi medida diretamente pela colocação de um microeletrodo no nervo fibular. O FSM foi medido pela técnica de pletismografia de oclusão venosa. O treinamento físico foi realizado três vezes na semana, em cicloergômetro, durante 60 minutos, entre o limiar anaeróbio e 10% do ponto de compensação respiratório, por 4 meses. Antes do período experimental, todos os parâmetros avaliados eram semelhantes entre os grupos. O treinamento físico reduziu significativamente a ANSM (-14 ± 3 impulsos/100batimentos, p<0,01) e aumentou o FSM (0,6 ± 0,1 ml.min-1.100ml-1, p<0,01). Adicionalmente, ocorreu um aumento significativo do VO2 pico (20 ± 6%, p=0,05) no grupo treinamento físico. ANSM, FSM e pico do VO2 não se alteraram nos pacientes com IC que permaneceram sedentários. Conclui-se que o treinamento físico reduz significativamente a ANSM em pacientes com IC em uso de carvedilol. Adicionalmente, os benefícios do treinamento físico sobre o FSM e a capacidade funcional são mantidos nestes pacientes. / Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure(HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity. The aim of study was to investigate whether exercise training in the presence of carvedilol maintains its beneficial effects on MSNA, forearm blood flow and functional capacity. Twenty seven HF patients, Functional Class II III(NYHA), EF<35%, peak VO2 <20ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training(n=15) and untrained(n=12). MSNA was recorded by microneurography. Forearm blood flow(FBF) was measured by venous occlusion plethysmography. The four-month training program consisted of three 60-min exercise/week on cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (-14 ± 3.3bursts/100HB, p<0.01) and increased FBF (0.6 ± 0.1 ml.min-1.100ml-1, p<0.01) in HF patients on carvedilol. In addition, exercise training improved peak VO2 in HF patients (20 ± 6%, p=0.05). MSNA, FBF and peak VO2 were unchanged in untrained HF patients on carvedilol. In conclusion, exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol.

Ding Baoguo. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 225-247). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.