No / Purpose: Evidence exists for an additional inhibitory accommodative control system mediated by the sympathetic branch of the autonomic nervous system (ANS). This work aims to show the relative prevalence of sympathetic inhibition in young emmetropic and myopic adults, and to evaluate the effect of sympathetic facility on accommodative and oculomotor function. Methods: Profiling of ciliary muscle innervation was carried out in 58 young adult subjects (30 emmetropes, 14 early onset myopes, 14 late onset myopes) by examining post-task open-loop accommodation responses, recorded continuously by a modified open-view infrared optometer. Measurements of amplitude of accommodation, tonic accommodation, accommodative lag at near, AC/A ratio, and heterophoria at distance and near were made to establish a profile of oculomotor function. Results: Evidence of sympathetic inhibitory facility in ciliary smooth muscle was observed in 27% of emmetropes, 21% of early-onset myopes and 29% of late-onset myopes. Twenty-six percent of all subjects demonstrated access to sympathetic facility. Closed-loop oculomotor function did not differ significantly between subjects with sympathetic facility, and those with sympathetic deficit. Conclusions: Emmetropic and myopic groups cannot be distinguished in terms of the relative proportions having access to sympathetic inhibition. Presence of sympathetic innervation does not have a significant effect on accommodative function under closed-loop viewing conditions.

Obesity is a growing disorder in the United States, affecting over 60% of the population. We previously defined sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT) using a viral transneuronal tract tracer. SNS innervation of WAT is the principle initiator of lipolysis, whereas decreases in sympathetic drive promote lipid accumulation. Which of the many origins of SNS outflow from brain to WAT results in SNS-mediated changes in lipid mobilization (increases in drive) or accumulation (decrease in drive) is unknown. Previous research indicates that sympathetic denervation blocks lipid mobilization; thus, rostral sites in the neuroaxis connected to WAT via the SNS may promote WAT lipid mobilization. The hypothalamic paraventricular nucleus (PVN) may play a role via its descending projections to the intermediolateral horn of the spinal cord. Therefore, the consequences of PVN lesions (PVNx) on WAT mobilization or accumulation were tested. PVNx resulted in increased lipid accumulation, indicated by increases in retroperitoneal (RWAT) , epididymal (EWAT) , and inguinal WAT (IWAT) pad masses, in fed hamsters, but PVNx did not block fasting (56 h)-induced lipid mobilization. Because adrenal medullary catecholamines, especially epinephrine, also play a minor role in lipid mobilization, we tested the contribution of catecholamine release on lipid mobilization through adrenal demedullation (ADMEDx), with and without PVNx, and found fastinginduced lipid mobilization was not blocked. There was, however, a suggestion that distal denervation of IWAT, with and without ADMEDx, partially blocked lipid mobilization. In addition, evidence suggests SNS also may be an important controller of fat cell proliferation. Surgical denervation of WAT triggers increases in fat cell number (FCN), but have not determined if this FCN increase is due to preadipocyte proliferation or differentiation of preadipocytes into mature fat cells. We also have not demonstrated what role sensory innervation may have in regulating white adipocyte proliferation. Therefore, the role of WAT sympathetic or sensory innervation on adipocyte proliferation was tested. The SNS but not sensory denervation triggered bona fide proliferation as indicated by bromodeoxyuridine plus AD3, a specific adipocyte membrane protein, colabeling. These and previous data suggest that the SNS plays a role in regulating adiposity.

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.

Sabe-se que a ativação do Sistema Nervoso Simpático (SNS) induz osteopenia via adrenoceptores b2 (b2-AR). Para investigar se o hormônio tireoideano (HT) interage com o SNS para regular a massa óssea, estudamos o efeito do HT em associação com isoproterenol ou propranolol (agonista e antagonista b-adrenérgicos) e avaliamos o efeito do HT em camundongos com elevado tônus simpático, devido à dupla inativação gênica do a2A-AR e a2C-AR (a2A/a2C-AR-/-), autorreceptores que inibem a liberação de noradrenalina. Vimos que esses animais apresentam um fenótipo de alta massa óssea, apesar do elevado tônus simpático e de intacta sinalização b2-adrenérgica, sugerindo que o a2A-AR e/ou a2C-AR, além do b2-AR, possam mediar ações do SNS no osso. O propranolol limitou e o isoproterenol acentuou os efeitos deletérios do HT no esqueleto, já os animais a2A/a2C-AR-/- apresentaram resistência à osteopenia induzida pela tireotoxicose, o que sugere que há interação entre SNS e o HT para regular a massa óssea, e que esta depende tanto do b2-AR como do a2A- e/ou a2C-AR. / It is known that the sympathetic nervous system (SNS) activation induces ostepenia, via b2-adrenoceptors (b2AR). To investigate if thyroid hormone (TH) interacts with the SNS to regulate bone mass, we studied the effect of TH in association with isoproterenol or propranolol (b-adrenergic agonist and antagonist) and evaluated the effect of TH in mice with a chronic elevated sympathetic tone, due to double disruption of a2A-AR and a2C-AR (a2a/a2c-AR-/-), autoreceptors that inhibit noradrenalin release. We showed that KO mice present a high bone mass phenotype in spite of an elevated sympathetic tone and of intact b2-adrenergic signaling, which suggests that a2A- and/or a2C-AR, besides b2-AR, may also mediate the SNS actions in the bone. Propranolol limited and isoproterenol accentuated the deleterious effects of TH in the skeleton, while a2A/a2C-AR-/- mice presented resistance to the T3-induced osteopenia, which suggest that there is an interaction between the SNS and TH to regulate bone mass, and that it is dependent on b2-AR and a2A-AR and/or a2C-AR signaling.

Sabe-se que a ativação do Sistema Nervoso Simpático (SNS) induz osteopenia via adrenoceptores b2 (b2-AR). Para investigar se o hormônio tireoideano (HT) interage com o SNS para regular a massa óssea, estudamos o efeito do HT em associação com isoproterenol ou propranolol (agonista e antagonista b-adrenérgicos) e avaliamos o efeito do HT em camundongos com elevado tônus simpático, devido à dupla inativação gênica do a2A-AR e a2C-AR (a2A/a2C-AR-/-), autorreceptores que inibem a liberação de noradrenalina. Vimos que esses animais apresentam um fenótipo de alta massa óssea, apesar do elevado tônus simpático e de intacta sinalização b2-adrenérgica, sugerindo que o a2A-AR e/ou a2C-AR, além do b2-AR, possam mediar ações do SNS no osso. O propranolol limitou e o isoproterenol acentuou os efeitos deletérios do HT no esqueleto, já os animais a2A/a2C-AR-/- apresentaram resistência à osteopenia induzida pela tireotoxicose, o que sugere que há interação entre SNS e o HT para regular a massa óssea, e que esta depende tanto do b2-AR como do a2A- e/ou a2C-AR. / It is known that the sympathetic nervous system (SNS) activation induces ostepenia, via b2-adrenoceptors (b2AR). To investigate if thyroid hormone (TH) interacts with the SNS to regulate bone mass, we studied the effect of TH in association with isoproterenol or propranolol (b-adrenergic agonist and antagonist) and evaluated the effect of TH in mice with a chronic elevated sympathetic tone, due to double disruption of a2A-AR and a2C-AR (a2a/a2c-AR-/-), autoreceptors that inhibit noradrenalin release. We showed that KO mice present a high bone mass phenotype in spite of an elevated sympathetic tone and of intact b2-adrenergic signaling, which suggests that a2A- and/or a2C-AR, besides b2-AR, may also mediate the SNS actions in the bone. Propranolol limited and isoproterenol accentuated the deleterious effects of TH in the skeleton, while a2A/a2C-AR-/- mice presented resistance to the T3-induced osteopenia, which suggest that there is an interaction between the SNS and TH to regulate bone mass, and that it is dependent on b2-AR and a2A-AR and/or a2C-AR signaling.

Thesis (M.S.)--Miami University, Dept. of Zoology, 2004. / Title from first page of PDF document. Includes bibliographical references (p. 36-47).

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

The aim of the present investigation was to study the influence of the sympathetic nervous system and of various adrenoceptor agents on enzyme secretion and morphology in rat parotid and guinea-pig submandibular glands. Biochemical methods were combined with electron microscopical techniques. Two different in vitro systems were employed, batch-incubation and microperifusion, to characterize the sympathetically evoked amylase release and its correlation to cyclic AMP. By using various selective β-adrenoceptor agonists and antagonists a dominance of the β1-adrenoceptor over the β2 - in regulating amylase release - was establ ished. Continuous noradrenaline perifusion caused a rapid initial amylase discharge, closely correlated to tissue levels of cyclic AMP; no correlation between the two was observed during the later phase. Prenalterol (a β1-agonist) failed to elevate glandular cyclic AMP. This was in contrast to its potent secretagogic effect. On the other hand, terbutaline (a β2-agonist) was a weak secretagogue but markedly raised the levels of cyclic AMP. Thus, β-adrenoceptor activation may lead to release of large amounts of amylase despite minimal or no increase in cyclic AMP. Moreover, these effects seemed to be dissociated in salivary glands with regard to the β-adrenoceptor subtypes. This was further substantiated by the findings that repeated injections of prenalterol induced qualitative changes in the granule populations, similar to those caused by the non-selective β-agonist isoprenaline. Terbutaline was without effect. However, acinar cells size was increased following both prenalterol and terbutaline treatment. The data suggest that the 3-adrenergic effects on acinar cell size and granule population may be independently regulated. A decreased sympathetic activity of long duration was induced by neonatal or adult extirpation of the superior cervical ganlion on one side. Acinar cell size, as well as granule and amylase content was reduced 9 weeks after neonatal denervation. Ganglionectomy performed in adult animals was without significant effects. The secretory behaviour of neonatally denervated glands was characterized by an increased postjunctional sensitivity to 3-adrenoceptor agonists. Of special interest was the finding that neonatal denervation seemed to transform terbutaline from a partial to a full secretory agonist, thus changing its effects in the direction of those of prenalterol and noradrenaline. Moreover, increased levels of cyclic AMP as well as an enhanced response to DBcAMP were noted in the denervated glands as were intracellular changes. The denervation supersensitivity after neonatal denervation seems to differ from that observed in adult denervated glands. The results of the studies on denervated glands suggest that the sympathetic nervous system plays a fundamental role in the early maturation of the rat parotid gland as well as for the development of the β-adrenoceptor subtypes. / <p>S. 1-34: sammanfattning, s. 35-128: 6 uppsatser</p> / digitalisering@umu

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