Abstract Neurogenic factors are known to be important in the development of hypertension. Our current knowledge of the role of autonomic nervous system in chronic hypertension is, however, limited. The purpose of the present study was to evaluate the possible abnormalities in heart rate variability (HRV) and baroreflex sensitivity (BRS) in patients with long standing systemic hypertension compared to subjects without evidence of cardiovascular disease. A particular aim was also to examine whether genetic variation in the renin-angiotensin-aldosterone system (RAS) genes have an influence on cardiovascular autonomic regulation. Case-control studies were carried out on a total of 280 normotensive and 214 hypertensive subjects drawn from a random middle-aged population originally recruited for an epidemiologic study of cardiovascular risk factors. The possible association of BRS with the genetic polymorphisms of renin-angiotensin-aldosterone system genes was studied in a cross-sectional study of 315 healthy controls. Genetic associations were also tested in a younger, independent population sample of 66 subjects. The effects of intensified antihypertensive treatment on autonomic cardiovascular control were evaluated in 33 hypertensive patients with poor blood pressure control. Wide interindividual variation in both HRV and BRS was observed in normotensive as well as hypertensive subjects. Overall HRV and autonomic responses to a change in body posture were blunted in long-standing hypertension. Decreased HRV was mainly related to elevated blood pressure and obesity. For the first time in a population-based study, it was confirmed that BRS is impaired in patients with long-standing hypertension despite adequate antihypertensive treatment. In contrast to HRV, BRS was reduced in hypertensive subjects also after adjustment for blood pressure and obesity. BRS also varied widely both between healthy and hypertensive individuals. The wide interindividual variation in the markers of autonomic cardiovascular regulation was not, however, completely explained by demographic variables, cardiovascular risk factors or lifestyle, suggesting a genetic component contributing to HRV and BRS. The polymorphism in the aldosterone synthase (CYP11B2) gene was found to strongly associate with BRS in two independent random populations of apparently healthy subjects. The association was even stronger in the younger population. On the basis of the observations made in the older population, it seems possible that women are protected against the effect of age and blood pressure on BRS and tend to maintain the genomic influence longer. Intensified antihypertensive combination therapy improved blood pressure control and caused regression of left ventricular hypertrophy, and resulted in significant improvements of HRV and BRS. The present study shows that HRV and BRS are altered in long-standing systemic hypertension. Together with age, blood pressure and obesity, genetic factors seem to be important determinants of BRS. However, abnormal autonomic cardiovascular regulation does not seem to be an irreversible phenomenon, but can be partly restored by modern combination antihypertensive therapy.

Maintenance of stable arterial blood pressure during orthostatic challenges is a major problem after spinal cord injury (SCI). Since early participation in rehabilitation is critically important in reducing long term morbidity, recovering the ability to regulate blood pressure during therapy is essential for individuals with SCI. The objective of our study was to investigate short term cardiovascular function of able-bodied (AB), paraplegic (PARA) and tetraplegic (TETRA) subjects in response to head up tilt (HUT) as an early indicator of autonomic damage that might forewarn of future orthostatic regulatory problems. We acquired cardiovascular variables from able-bodied (AB; n=11), paraplegic (PARA; n=5) and tetraplegic (TETRA; n=5) subjects in response to HUT. The SCI patients in both groups were in their first two months post injury. Data were recorded at rest and during 7 min each at 20??, 40??, 60?? and 80?? HUT. Techniques used to estimate regulatory capability and reflex activity included: Mean values and spectral power of heart rate (HR) and arterial blood pressure (BP), baroreflex sequence measurements and cross correlation between HR and systolic blood pressure (SBP). An index of baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), and the percentage occurrence of systolic blood pressure (BP) ramps and baroreflex sequences were calculated from baroreflex sequence measurements. The spectral power of HR and BP, the cross correlation of systolic BP and heart rate (HR) were examined in low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) ranges. The BRS index was significantly (p andlt; 0.05) decreased from supine to 80o HUT in AB and TETRA. This index in PARA was the lowest at each tilt position in the three groups, and decreased with tilt. The percentage of heart beats involved in systolic BP ramps and in baroreflex sequences significantly (pandlt;0.05) rose from supine to 80o HUT in AB, was relatively unchanged in PARA and declined in TETRA. Both of these indexes were significantly (pandlt;0.05) lowerin the SCI than in the AB group at each tilt level. The BEI values were greatest in AB, and declined with tilt in all groups. Spinal cord injured patients had less power of BP and HR fluctuations than AB in both LF and HF regions. The LF spectral power of BP and HR increased with tilt in AB, remained unchanged in PARA and decreased in TETRA. The HF spectral power of HR decreased in all three groups. The peak HR / BP cross correlation in the LF region was greatest in AB, and significantly (pandlt;0.05) increased during HUT in AB, remained fairly constant in PARA, and declined in TETRA. The peak cross correlation in the HF region significantly (pandlt;0.05) decreased with tilt in all groups, and the SCI group had lower values than AB at each tilt level. We conclude that both PARA and TETRA had a smaller percentage of SBP ramps, BRS, and lower BEI than AB, likely indicating decreased stimulation of arterial baroreceptors, and less engagement of feedback control. The mixed sympathetic, parasympathetic innervations of paraplegics, or their elevated HR, may contribute to their significantly lower BRS. Our data indicate that the pathways utilized to evoke baroreflex regulation of HR are compromised by SCI and this loss may be a major contributor to the decrease in orthostatic tolerance following injury.

Motivation: Abdominal obesity (hereafter referred to as "obesity") is becoming the biggest "global epidemic" of our modern times. It is associated with a range of diseases, including cardiovascular diseases and hypertension. Recent research showed that an increase in sympathetic activity is of central importance in the pathogenesis of obesity-related diseases. Increased leptin levels and impaired baroreflex sensitivity have both been independently associated with abdominal obesity and increased sympathetic activity. A perception of poorer health may also contribute to the physiological characteristics of obesity-related diseases. A lack of data regarding sympathetic activity, leptin levels, baroreflex sensitivity and perception of health in Africans, serves as a motivation for conducting this study. Objective: To investigate the contributions of leptin levels, baroreflex sensitivity and perception of health data to increased sympathetic activity in lean and obese African women from South Africa. Methodology: The manuscript presented in Chapter 2 made use of the data obtained in the POWIRS (Profiles of Obese Women with the Insulin Resistance Syndrome) study. A group of 102 urbanized African women, living in the North-West Province of South Africa, was recruited according to body mass indexes. Only 85 subjects were included for analysis due to incomplete datasets. For this study, subjects were divided into lean and obese groups according to their waist circumferences. Anthropometric measurements were done according to standardized methods. Resting cardiovascular measurements were obtained from Finometer observations. Resting, fasting levels of leptin were calculated after radioimmunoassay analyses. Subjective perception of health was determined by means of the 28-item General Health Questionnaire. Comparisons between the groups were done using analysis of covariance (ANCOVA) whilst adjusting for cardiovascular risk factors (age. smoking, alcohol consumption and physical activity). Correlation coefficients were determined to indicate any associations between leptin, baroreflex sensitivity and perception of health with sympathetic activity (represented by heart rate) and other cardiovascular variables. The study was approved by the Ethics committee of the North-West University and all the subjects gave informed consent in writing. The reader is referred to the Methods section in Chapter 2 for a more detailed description of the subjects, study design and analytical procedures used in this dissertation. Results and conclusion: Results from this study indicate that obese African women, compared to lean African women, were older, reported higher physical activity, and exhibited higher diastolic and mean blood pressure, heart rate, cardiac output, arterial compliance, leptin and hypertension prevalence rate values. In lean African women social dysfunction was positively associated with diastolic and mean blood pressure and arterial resistance, and negatively with arterial compliance. In obese African women baroreflex sensitivity was negatively associated with diastolic blood pressure, which could be an indication of impaired baroreflex sensitivity. In this obese group a perception of social dysfunction was associated with decreased heart rate. Although leptin and heart rate were significantly higher in the obese Africans, no significant correlations existed between these variables to reflect leptin's enhancement of sympathetic activity. However, leptin correlated weakly but positively with cardiac output (p = 0.054, r = 0.32). In conclusion, baroreflex sensitivity (although similar between groups) and leptin seem to contribute to blood pressure and thus hypertension in obese African women, possibly through increased sympathetic activity and volume loading. A perception of poorer health, especially a perception of social dysfunction, could possibly contribute to this image. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2007.

Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2007.

Motivation: Abdominal obesity (hereafter referred to as "obesity") is becoming the biggest "global epidemic" of our modern times. It is associated with a range of diseases, including cardiovascular diseases and hypertension. Recent research showed that an increase in sympathetic activity is of central importance in the pathogenesis of obesity-related diseases. Increased leptin levels and impaired baroreflex sensitivity have both been independently associated with abdominal obesity and increased sympathetic activity. A perception of poorer health may also contribute to the physiological characteristics of obesity-related diseases. A lack of data regarding sympathetic activity, leptin levels, baroreflex sensitivity and perception of health in Africans, serves as a motivation for conducting this study. Objective: To investigate the contributions of leptin levels, baroreflex sensitivity and perception of health data to increased sympathetic activity in lean and obese African women from South Africa. Methodology: The manuscript presented in Chapter 2 made use of the data obtained in the POWIRS (Profiles of Obese Women with the Insulin Resistance Syndrome) study. A group of 102 urbanized African women, living in the North-West Province of South Africa, was recruited according to body mass indexes. Only 85 subjects were included for analysis due to incomplete datasets. For this study, subjects were divided into lean and obese groups according to their waist circumferences. Anthropometric measurements were done according to standardized methods. Resting cardiovascular measurements were obtained from Finometer observations. Resting, fasting levels of leptin were calculated after radioimmunoassay analyses. Subjective perception of health was determined by means of the 28-item General Health Questionnaire. Comparisons between the groups were done using analysis of covariance (ANCOVA) whilst adjusting for cardiovascular risk factors (age. smoking, alcohol consumption and physical activity). Correlation coefficients were determined to indicate any associations between leptin, baroreflex sensitivity and perception of health with sympathetic activity (represented by heart rate) and other cardiovascular variables. The study was approved by the Ethics committee of the North-West University and all the subjects gave informed consent in writing. The reader is referred to the Methods section in Chapter 2 for a more detailed description of the subjects, study design and analytical procedures used in this dissertation. Results and conclusion: Results from this study indicate that obese African women, compared to lean African women, were older, reported higher physical activity, and exhibited higher diastolic and mean blood pressure, heart rate, cardiac output, arterial compliance, leptin and hypertension prevalence rate values. In lean African women social dysfunction was positively associated with diastolic and mean blood pressure and arterial resistance, and negatively with arterial compliance. In obese African women baroreflex sensitivity was negatively associated with diastolic blood pressure, which could be an indication of impaired baroreflex sensitivity. In this obese group a perception of social dysfunction was associated with decreased heart rate. Although leptin and heart rate were significantly higher in the obese Africans, no significant correlations existed between these variables to reflect leptin's enhancement of sympathetic activity. However, leptin correlated weakly but positively with cardiac output (p = 0.054, r = 0.32). In conclusion, baroreflex sensitivity (although similar between groups) and leptin seem to contribute to blood pressure and thus hypertension in obese African women, possibly through increased sympathetic activity and volume loading. A perception of poorer health, especially a perception of social dysfunction, could possibly contribute to this image. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2007.

Made available in DSpace on 2016-08-17T18:39:51Z (GMT). No. of bitstreams: 1 6222.pdf: 2879821 bytes, checksum: 010a3c6abf3b0c6f2ec81ebf9ff59ef0 (MD5) Previous issue date: 2014-08-21 / Universidade Federal de Sao Carlos / Aging causes changes in several human subsystems such as the cardiovascular and immune systems. The objective of this study was to evaluate the relationship between baroreflex function through linear algorithm (cross-spectral analysis) and proinflammatory cytokines in the aging process and also assess the baroreflex sensitivity, TNF-α, IL-6 and hsCRP in different ages and in the aging process. One hundred and ten apparently healthy subjects divided into 5 groups with 22 individuals each, according to age were evaluated: 21-30 years, 30-40 years, 40-50 years, 50-60 years, 60-70 years. The experimental protocol consisted of a blood samples collection for analysis of inflammatory markers and in the same day were collected ECG, blood pressure and respiratory movements for 15 minutes in the supine position and in standing position, after the active postural change for 15 minutes. For the analysis of baroreflex sensitivity cross spectral analysis (coherence, phase and gain) was used and ELISA method for analysis of TNF-α and IL-6 was used. Data were analyzed using analysis of variance one-way ANOVA test with Tukey test post-hoc or Kruskal-Wallis oneway ANOVA with Dunn's post-hoc according to the normality of the data and the Spearman correlation test. The level of significance for the tests was 5%. The main results were: 1) reduced baroreflex sensitivity during the aging process; 2) increased levels of inflammatory markers in the aging process; 3) negative correlation between IL-6 and BF gain and phase; 4) negative relationship between hsCRP and coherence, phase and gain in BF. It can be concluded that the human natural aging causes a loss of baroreflex sensitivity and increased serum levels of inflammatory markers studied, although the decrease in baroreflex sensitivity as function of the decreasing of vagal autonomic function occurred in the 41-50 age range, and only in the next age was observed changes in inflammatory markers. / O envelhecimento causa alterações em diversos subsistemas humanos como o cardiovascular e imunológico. O objetivo deste trabalho foi avaliar a relação entre a função barorreflexa, por meio de algoritmo linear (análise espectral cruzada) e citocinas próinflamatórias no processo de envelhecimento e ainda, avaliar a sensibilidade barorreflexa, IL- 6, TNF-α e PCRus em diversas faixas etárias e no processo de envelhecimento. Foram avaliados 110 indivíduos aparentemente saudáveis divididos em 5 grupos com 22 indivíduos cada, de acordo com a faixa etária: 21-30 anos, 30-40 anos, 40-50 anos, 50-60 anos, 60-70 anos. O protocolo experimental consistiu em uma coleta de amostras de sangue para a análise dos marcadores inflamatórios e no mesmo dia foram coletados o eletrocardiograma (ECG), a pressão arterial de pulso e a respiração por 15 minutos na postura supina, logo após foi realizada a mudança postural ativa de supino para ortostatismo, permanecendo 15 minutos nesta posição a coleta de sangue. Para a análise da sensibilidade barorreflexa foi utilizada a analise espectral cruzada e o método ELISA para análise das citocinas TNF-α e IL-6. Os dados foram analisados por meio do teste de análise de variância ANOVA one-way com posthoc de Tukey ou Kruskal-Wallis ANOVA one-way com post-hoc de Dunn s de acordo com a normalidade dos dados e teste de Correlação de Spearman. O nível de significância estabelecido para os testes foi de 5%. Os principais resultados foram: 1) redução da sensibilidade barorreflexa durante o processo de envelhecimento; 2) aumento dos níveis dos marcadores inflamatórios no processo de envelhecimento; 3) relação negativa entre a IL-6 e fase e ganho em BF; 4) relação negativa entre PCRus e coerência, fase e ganho em BF. Podese concluir que o envelhecimento natural humano causa a redução da sensibilidade barorreflexa e aumento dos níveis séricos dos marcadores inflamatórios estudados, ainda a diminuição da sensibilidade barorreflexa em consequência da diminuição da função autonômica vagal correu na faixa etária 41-50 e somente na faixa etária seguinte foi observada alterações nos marcadores inflamatórios.

Submitted by LUIZ HENRIQUE NATALI null (luhnatali@hotmail.com) on 2016-08-30T19:05:39Z No. of bitstreams: 1 DISSERTAÇÃO completa.pdf: 1855365 bytes, checksum: e1aaabe0f34e47039840d7783425d449 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-08-31T16:37:51Z (GMT) No. of bitstreams: 1 natali_lh_me_araca.pdf: 1855365 bytes, checksum: e1aaabe0f34e47039840d7783425d449 (MD5) / Made available in DSpace on 2016-08-31T16:37:51Z (GMT). No. of bitstreams: 1 natali_lh_me_araca.pdf: 1855365 bytes, checksum: e1aaabe0f34e47039840d7783425d449 (MD5) Previous issue date: 2016-08-01 / A hipertensão arterial é frequentemente associada à prejudicada sensibilidade do barorreflexo (SBR). Em ratas espontaneamente hipertensas (SHR), a gravidez reduz a pressão sanguínea, e este efeito tem sido associado ao aumento da biodisponibilidade de óxido nítrico (NO). O aumento da biodisponibilidade do NO tem sido associado a uma SBR restaurada em animais hipertensos. Por isso, testamos a hipótese de que a gravidez melhora a SBR em SHR. Foram realizados experimentos em ratas Wistar e SHR não prenhas (NP) e prenhas (P), sendo dez virgens e dez prenhas em cada grupo, para avaliar a modulação autonômica cardíaca e vasomotora, a SBR em condições basais (espontânea) e após a administração de doses de fenilefrina (FE) e nitroprussiato de sódio (NPS). Séries temporais com valores de intervalo de pulso (IP) e de pressão arterial sistólica (PAS) foram geradas e tiveram espectros calculados pela Transformada Rápida de Fourrier. Em seguida, os espectros foram integrados em bandas de baixa (LF) e alta freqüência (HF), e os poderes das bandas foram tomadas como índices de modulação autonômica cardiovascular. Observamos reduzida pressão arterial média em ratas Wistar prenhas (W-P) e SHR prenhas (SHR-P) quando comparado com ratas NP, no entanto, a frequência cardíaca basal não foi alterada. Em SHR-NP, a análise espectral revelou modulação autonômica cardiovascular alterada quando comparado com os outros grupos (banda de alta LF do espectro PAS e banda de alta HF dos espectros IP). No entanto, em SHR-P os parâmetros autonômicos foram encontrados semelhantes aos observados em ratas Wistar-NP, sugerindo que a prenhez restaurou as alterações na modulação autonômica. A SBR espontânea não foi alterada em SHR-P quando comparado com W-P. A prenhez reduziu a SBR durante situações de hipotensão no grupo Wistar. A SBR avaliada após a administração de FE ou NPS foi menor em SHR-NP em comparação com Wistar-NP, e não se alterou pela prenhez. Em conclusão, a gravidez não melhorou as SBR em SHR, mas normalizou a alterada modulação vasomotora simpática e a modulação parassimpática cardíaca observados em SHR-NP. / Hypertension is frequently associated to impaired baroreflex sensitivity (BRS). In spontaneously hypertensive rats (SHR), pregnancy reduces blood pressure, and this effect has been associated to increased nitric oxide (NO) availability. Increased NO bioavailability has been linked to improved BRS in hypertensive animals. Therefore, we tested the hypothesis that pregnancy improves the BRS in SHR. Experiments were performed to evaluate the vasomotor and cardiac autonomic modulation, and the BRS at baseline conditions (spontaneous) and after phenylephrine (PE) and sodium nitroprusside (SNP) administrations in female non-pregnant (NP) and pregnant (P) Wistar rats and SHR. Time series with pulse interval (PI) and systolic arterial pressure (SAP) values were generated and had spectra calculated by Fast Fourier Transform. Next, spectra were integrated into low (LF) and high frequency (HF) bands, and the powers of the bands were taken as indexes of cardiovascular autonomic modulation. Reduced mean arterial pressure was observed in Wistar pregnant (W-P) and SHR pregnant (SHR-P) when compared to NP matched rats, however the heart rate was not altered. In SHR-NP, spectral analysis revealed altered cardiovascular autonomic modulation when compared to the other groups (high LF band of the SAP spectra and high HF band of the PI spectra). However, in SHR-P the autonomic parameters were found similar to those observed in Wistar-NP, suggesting that pregnancy prevented changes in autonomic modulation. Spontaneous BRS was not altered in SHR-P when compared to W-P. Pregnancy reduced the BRS during hypotension in Wistar group. BRS assessed with PE and SNP administration was found lower in SHR-NP as compared to Wistar-NP, and it was not altered by pregnancy. In conclusion, pregnancy did not improve the BRS in SHR but normalized altered sympathetic vasomotor modulation and parasympathetic cardiac modulation in SHR.

No description available.

Baroreflex sensitivity (BRS) is often reduced in elderly populations and patients with chronic cardiovascular diseases leading to a concomitant rise in blood pressure variability (BPV) that is associated with increased cardiovascular related morbidity and mortality. Thus, there is a need to better understand the mechanisms by which BPV causes cardiovascular end-organ damage. Animal studies using sinoaortic denervation (SAD) to increase BPV have demonstrated pathologic changes in the structure of the heart and blood vessels; however, there is a paucity of data investigating changes in functional measures of the heart and smaller, resistance type arteries. Furthermore, the pathogenic mechanisms involved in BPV-induced cardiovascular end-organ damage remain unknown. Baroreceptor denervation results in multiple cardiac stressors, many of which are associated with production of reactive oxygen species. Oxidative stress is known to promote cardiovascular end-organ damage but it is unclear if it plays a role in models of increased BPV. Thus, this study was designed to investigate the functional responses of smaller resistance type arteries and the heart to chronic exposure to enhanced BPV. In addition, the role of oxidative stress on these functional responses in a normotensive rat model of increased BPV was also investigated. Rats were subjected to either SAD surgery or a sham procedure and were observed for six weeks. To determine the role of oxidative stress, SAD rats were either treated with the superoxide dismutase mimetic tempol or left untreated. During the observation period, mean blood pressure remained normotensive, whereas baroreflex sensitivity was reduced and BPV increased two to three fold. Weekly in vivo assessment of vascular function of the long posterior ciliary artery (LPCA) demonstrated a significant reduction in endothelial-dependent dilation starting three weeks after SAD surgery compared to the sham group. Endothelial-independent dilation was not affected by SAD. Structural changes were not evident in the LPCA following SAD. However, structural (wall thickness, wall area, and wall area/lumen area ratio) and functional (strain and distensibility) changes were observed in the aorta. Cardiac structural (hypertrophy) and functional (diastolic dysfunction) effects were also evident following six weeks of increased BPV. Antioxidant treatment with tempol did not have any effect on the SAD-induced increase in BPV or decrease in BRS. Nevertheless, chronic tempol treatment prevented or reduced the cardiovascular end-organ damage (endothelial-dependent vascular dysfunction, decreased aortic distensibility, cardiac and vascular hypertrophy, and cardiac dysfunction) observed in the untreated SAD group. These findings suggest that the pathology observed following SAD is at least partly mediated by oxidative stress. Antioxidant treatment in patients with increased BPV (e.g., hypertension, diabetes, heart failure) may prevent or ameliorate cardiovascular end-organ damage and reduce the overall risk for cardiovascular disease events.

The aim of this diploma thesis was to get familiar with methods to generate surrogates and how to apply them on cardiovascular signals. The first part of this diploma thesis describes the basic theory of baroreflex function and methods to generate surrogate data. Surrogate data were generated from data, acquired from the database, by using three different methods. In the next part of this diploma thesis, coherence significance between blood pressure and heart intervals was calculated by using surrogates. In the end two hypotheses were defined and tested by which it was detected whether the orthostatic change of the measurement position has effect on the causal coherence change and baroreflex function.