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Hypertension, or chronic blood pressure elevation, affects approximately a third of American adults and is responsible for $70 billion dollars annually in medical costs. Recent studies have attempted to identify genetic variants that influence cardiopulmonary function, including blood pressure regulation. This study seeks to determine whether a polymorphism in position -182 of the gene encoding the phenylethanolamine N-methyltransferase (PNMT) enzyme, which converts norepinephrine to epinephrine, influences catecholamine levels and cardiovascular function. Secondly, this study seeks to explore whether a polymorphism at amino acid position 16 of the beta-2 adrenergic receptor (B2AR) affects the cardiovascular response to albuterol in healthy individuals; this study also explores the pulmonary response to albuterol in healthy subjects and patients with cystic fibrosis according to B2AR genotype. All subjects were genotyped and stratified according to genotype. Baseline measurements were taken. Albuterol was administered via nebulizer. Cardiopulmonary measurements were taken again at 30-, 60-, and 90- minutes post-albuterol administration. This study found that the PNMT polymorphism at position -182 influences circulating epinephrine, the epinephrine:norepinephrine ratio, and cardiac output. The B2AR polymorphism at amino acid position 16 affects the percent change in systemic vascular resistance in response to albuterol administration in healthy subjects. Furthermore, this study found that the B2AR polymorphism at amino acid 16 affects the change in forced vital capacity following albuterol administration in cystic fibrosis subjects.

Motivation: The prevalence of obesity is the highest among African women in South Africa. Since obesity is a major cardiovascular risk factor, African women in South Africa could be regarded as a high risk group. However, investigations on obesity-related hypertension are limited in this population group. The associations of body fat distribution and hormones such as leptin and endothelin-1 with cardiovascular function have not yet been determined in these women. It has been determined that endothelin-1 is a role player in the development and/or maintenance of hypertension in various population groups, especially African Americans. Endothelin-1 has also been found to be involved in obesity-related hypertension in non-African population groups. It has been indicated that the obesity-related hormone, leptin, also plays a role in obesity-related hypertension, especially in African Americans. Leptin levels have been found to be higher in obese hypertensive African American women compared to an obese normotensive control group. Since the above-mentioned two hormones playa prominent role in obesity and hypertension in African American and non-African population groups, the lack of data on African women in South Africa serves as motivation to conduct this investigation. Aim: To investigate obesity-related hypertension in African women through the determination of associations between various anthropometric and endocrinological variables with cardiovascular, especially vascular function. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of data from the POWIRS (Profiles of Obese Women suffering from the Insulin Resistance Syndrome) I project where African women were selected from a government institution in the North West Province. A group of 98 women were divided into lean normotensive, overweight/obese normotensive and overweight/obese hypertensive groups. Anthropometric and cardiovascular measurements were taken and the lipid profile, leptin and endothelin-1 levels determined. The analysis of covariance (ANCOVA) was used to show significant differences between groups while adjusting for age. Partial correlation coefficients were used to show associations between various variables while adjusting for age. Stepwise linear regression analysis was also used to show associations between variables. The study presented in Chapter 5 made use of both POWIRS I and II, which are studies including Africans and Caucasians, respectively. The methodology of the two studies was the same. All subjects gave informed consent in writing and the Ethics Committee of the North-West University approved the study. The reader is referred to the "Materials and Methods" section of Chapters 2-5 for a more elaborate description of the subjects, study design and analytical methods used in each article. vii Results and conclusions of the individual manuscripts > Results from Chapter 2 showed that the volume loading effect associated with obesity was present in both overweight/obese normotensive and overweight/obese hypertensive groups, however, the accommodating effect observed in the overweight/obese normotensive group was absent in the overweight/obese hypertensive group due to decreased vascular function. This was confirmed by a high pulse pressure. Decreased vascular functioning was associated with the abdominal skin fold. This suggests that abdominal subcutaneous fat may either be a marker of visceral fat, or may in itself contribute to increased cardiovascular risk in Africans. > Results from Chapter 3 showed a negative result. Plasma endothelin-1 levels were similar for the lean normotensive, overweight/obese normotensive and overweight/obese hypertensive groups. After re-dividing the groups into normotensive and hypertensive, and then into lean and overweight/obese, still no differences could be obtained. Additionally, no correlations could be obtained between endothelin-1 and cardiovascular function in any of the groups. These findings suggest that endothelin-1 is not implicated in obesity-related hypertension in African women. > In Chapter 4, leptin levels were elevated in both overweight/obese normotensive and hypertensive groups compared to the lean normotensive group. However, leptin levels did not differ between the two overweight/obese groups. Even though leptin levels were the same, leptin was directly and positively associated with systolic blood pressure and pulse pressure and negatively with arterial compliance only in the overweight/obese hypertensive group, independent of obesity, insulin resistance, hyperinsulinemia and age. > In Chapter 5 the volume loading, as well as the accommodating effect, that is, decreased total peripheral resistance and increased arterial compliance, was present in both African and Caucasian obese groups compared to their lean controls. Even though leptin levels, body mass index and age were similar for both African and Caucasian obese groups, the accommodating effect seemed to be more prominent in the obese Caucasian group, explaining a lower diastolic blood pressure compared to the obese African group. Leptin showed a favourable negative association with diastolic blood pressure and total peripheral resistance in the obese Caucasian group, but not in the obese African group. This may indicate that leptin predominantly exerts pathological influences on obese African women, as determined previously in Chapter 4. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.

Context: Although the long-term goal of antihypertensive therapy is to reduce adverse clinical outcomes, the only way to evaluate the efficacy of treatment in an individual is the magnitude of blood pressure (BP) reduction. ACE inhibitors and angiotensin receptor blockers (ARBs) are two drug classes that, by different mechanisms, inhibit the renin-angiotensin- aldosterone system that regulates BP. As these drugs are widely prescribed for hypertension, it is essential to determine and compare their effects on BP, heart rate and tolerability. Objectives: 1) To determine the dose-related effect of ACE inhibitors and ARBs on BP, heart rate and withdrawals due to adverse effects (WDAE), compared with placebo in the treatment of primary hypertension (SBP ≥ 140 mm Hg and/or ≥ DPB 90 mm Hg); and 2) To compare the relative effect on BP, heart rate and WDAE of a) each ACE inhibitor with other ACE inhibitors, b) each ARB with other ARBs, and c) all ACE inhibitors with all ARBs. Methods: Two systematic reviews of published, double-blind, randomized, controlled trials (RCTs) evaluating the BP lowering efficacy of fixed dose monotherapy with an ACE inhibitor or ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension were conducted. Electronic databases were searched for RCTs and similar trial inclusion criteria and methods of analysis were used in both reviews. Results: Ninety two RCTs evaluated the dose-related BP lowering efficacy of 14 ACE inhibitors in 12 954 participants with a baseline BP of 157.1/101.2 mm Hg. Forty six RCTs evaluated the dose-related BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 155.6/101.0 mm Hg. The best estimate of the near maximal trough BP reduction for ACE inhibitors and ARBs was -8/-5 mm Hg and -8/-5 mm Hg, respectively. ACE inhibitors and ARBs do not affect heart rate. The evidence for short-term WDAE (tolerability) was incomplete and weak and did not demonstrate a difference between the two classes of drugs. Conclusion: ACE inhibitors and ARBs are not different individually or as drug classes in BP lowering efficacy.

The purpose of the study was to examine psychological and methodological factors which would predict the white coat effect (WCE). The WCE is defined as the difference (mm Hg) between ambulatory and office measured blood pressure (BP). Sixty three community volunteers participated in this study. Participants were divided into 3 Response style groups: (1) Office responders had ambulatory BP values which were lower than office BP, (2) Non responders showed a minimal difference between office and ambulatory BP, and (3) Home responders had significantly higher ambulatory BP compared to office BP. Participants were asked to have a series of BP readings taken by a physician, nurse and by themselves and participate in 24 hour ambulatory monitoring. State and trait self-report psychological measures were completed. Self measured BP was the most representative of ambulatory BP for the sample as a whole, and in particular for the Home responders. State anxiety, previously dismissed as mediating factor in the expression of the white coat effect, proved to discriminate between the groups. Office responders had significantly higher levels of state anxiety, directly related to BP measurements, compared to Home and Non responders. Habituation to the experience of having BP measured by a physician, and habituation of the anxiety prior to the BP measurement, was different among the three groups. Trait psychological variables did not distinguish group membership. Self measured systolic BP, state anxiety prior to self measured BP, habituation to physician measured BP and the anxiety preceding it, were entered as predictors variables in a discriminant function analyses. These variables were able to correctly classify group membership for 63% of the sample.

There is evidence that non-surgical treatment of OSA improves blood pressure (BP) in patients with obstructive sleep apnea (OSA). The objective of this study is to determine the effect of maxillomandibular advancement (MMA) surgery for OSA on BP. 15 patients undergoing MMA surgery for treatment of OSA were enrolled. Ambulatory BP, and BMI were recorded pre- and post-operatively. The average age of the patients was 48.9 years and they had mean preoperative AHI of 40.8 and a mean baseline BMI of 30.8 kg/m2. There were no statistically significant reductions in mean systolic or diastolic BP postoperatively. The BMI was found to decrease on average from 30.8 kg/m2 to 29.3 kg/m2 at follow up (p = 0.01). There were no identifiable relationships between OSA severity and BP. Given the prevalence of OSA and it’s adverse medical consequences, more studies to determine the effect of MMA on BP are warranted.

Introduction and Purpose: In chronic heart failure (CHF), exercise rehabilitation results in a reduced risk of mortality, decreased disease severity, and increased functional ability. Resistance training is an important component of cardiac rehabilitation; however, an optimal training velocity that produces physiological and functional benefits at minimal perceived exertion and cardiovascular stress has yet to be identified. CHF patients need to be very efficient and perform the exercise that will give them the greatest benefits because of their poor exercise tolerance and increased risk of cardiovascular complications during exercise. In older populations, high velocity resistance training results in greater improvements in functional ability than low velocity resistance training. The use of high velocity resistance training in patients with CHF has yet to be examined; however it may enhance higher velocity activities of daily living while using a lower training load. The lower load associated with high velocity training may be less strenuous and result in lower cardiovascular stress, whilst maintaining a relatively similar power output compared to traditional low-velocity training. The purpose of this study was to compare the acute cardiovascular responses and perceived exertion of high and low velocity resistance exercises. Methods and Measures: 6 male and 1 female patients with systolic heart failure (CHF NYHA Class I-III) were recruited to perform two separate, randomly assigned exercise sessions. These sessions consisted of 5 exercises (hack squat, chest press, knee flexion, lat pull down and knee extension); one with a low velocity of contraction (3 second concentric phase: 3 second eccentric phase at 50% of the slow velocity 1-RM) and one with a high velocity (1 second concentric phase: 3 second eccentric phase at 50% of the high velocity 1-RM). During both sessions, heart rate, blood pressure, and a rating of perceived exertion (RPE) were obtained after the completion of each exercise. Results: Despite a similar relative mechanical load, the high velocity workout produced significantly lower systolic blood pressure (121.2 vs. 132.8 mmHg), mean arterial pressure (87.8 vs. 93.5), and RPE (3.7 vs.4.8) than the low velocity workout (p<0.05). The high velocity workout was not significantly different from the low velocity workout for heart rate, rate pressure product and diastolic blood pressure. Conclusion: We conclude that the high velocity workout produces more favourable blood pressure responses to resistance training in patients with CHF than the low velocity workout and may be used to enhance functional outcomes in cardiac rehabilitation programs.

The World Health Organization (WHO) states that iron deficiency (ID) is the preeminent global micronutrient deficiency. Maternal ID is linked to cardiovascular disease and hypertension in offspring, and yet the impact of ID on the kidney is not known. We characterized the impact of ID on circulating and tissue levels of iron and renal function. Seven and ten week old male and female Wistar rats were fed either control (270ppm) or low iron (3ppm) diet for ten weeks. Total, non-heme and heme iron levels in liver, kidney cortex and kidney medulla were measured following the dietary period. Hematocrit decreased most in males regardless of age (Male 7-17wk: 47%→ 31%; 10-20wk: 47%→ 33.5%; Female 7-17wk: 47%→ 34%; 10-20wk: 47%→ 39%). Dietary ID markedly decreased liver and kidney cortex non-heme iron in both males and females (Female: liver-178±25 to 21±7 ppm; kidney cortex-51±9 ppm to 10±1 ppm; Male: liver-102±18 ppm to 11±1 ppm; kidney cortex 36±14 to 15±8 ppm). In contrast, non-heme iron in the kidney medulla was not significantly decreased Secondly, in order to determine the impact of ID on renal function, blood pressure was monitored using radio-telemetry starting at six weeks of age (~175g body weight). Dietary salt challenge (5 days Low5 days HighNormal) was administered to all animals (n=16) starting at eight weeks of age. At ten weeks rats were assigned to either control (225pm) or low (3ppm) iron diet. Dietary salt challenge was repeated at 13 and 18 weeks of age respectively. Despite significant lowering of hematocrit (Control 45%  Low iron 38.6%) hemodynamic changes were minimal, in that, although blood pressure was lowered following ten weeks of dietary iron restriction, blood pressure did not change in response to dietary salt (Control MAP:105.0 ± 2.5mmHg; ID MAP:100.6 ± 3.2mmHg ). Collectively the tissue and functional analyses demonstrate that the body adapts to lowering of tissue iron supply with ID. The relative sparing of non-heme iron in the kidney medulla suggests that iron in this region of the kidney may be spared because of its importance in the systems responsible for regulating fluid and sodium balance. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2007-07-18 12:00:09.853

To optimize muscle blood flow to the skeletal muscle during exercise, the vascular bed of the muscle is partially protected from sympathetic nervous activity (SNA) vasoconstriction via a phenomenon termed functional sympatholysis. Functional sympatholysis has been documented during exercise periods in human skeletal muscle. However, it remains unknown whether functional sympatholysis is specific to the exercising period, or if it may persist for a period of time following skeletal muscle exercise. Through this study, we aimed to confirm the presence and duration of post-exercise functional sympatholysis in the human skeletal muscle. The cold pressor test (CPT) was administered to 9 male (mean age = 21.1 ± 0.8 years) participants at various time points during four different experimental trials (Rest, Exercise, Recovery 1 and Recovery 2). Exercise consisted of 7 minutes of moderate isometric handgrip exercise (15% below critical power). Heart rate (HR) and mean arterial pressure (MAP) were recorded continuously throughout each trial. Brachial artery mean blood velocity measurements as well as brachial artery diameter measurements were recorded on each participant’s exercising arm throughout each trial. Deep venous blood samples were drawn pre- and post-CPT administration from a catheter inserted into an antecubital vein of each participant’s non-experimental arm. The cardiovascular response to the CPT was repeatable across experimental days as it consistently resulted in MAP elevations regardless of the experimental time point of administration. The CPT also resulted in a significant elevation in plasma norepinephrine concentration from 0.49 ± 0.04 ng/mL at “pre-CPT” measurement to 0.66 ± 0.05 ng/mL at the end of the CPT in the Rest trial (P < 0.05). The percentage reduction in forearm vascular conductance (FVC) due to CPT administration during Exercise (4.5 ± 6.6%) and Recovery 1 (4 minutes post-exercise; -11.6 ± 8.8%) was significantly blunted in comparison to that measured during Rest (-34.8 ± 7.4%) (P < 0.05). The percentage change in FVC during the Recovery 2 trial (10 minutes post-exercise; -20.1 ± 7.1%) was not significantly different from that measured at Rest. These findings support the concept of a lingering presence of functional sympatholysis 4 minutes, but not 10 minutes, post-moderate exercise. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2011-12-21 17:17:09.037

The evidence for an increase in resting vagal tone to explain the lower heart rate of endurance athletes remains controversial. This study used spectral analysis of heart rate (HRV) and blood pressure (BPV) variability to examine the vagal and sympathovagal influences on the sinus node in 12 endurance-trained athletes (A) and 10 age and sex-matched control subjects (C) (age: 26(1.2) yrs; VO2max: A: 68.2(2.1) vs C: 41.4(2.0) ml/kg/min; p $<$ 0.05). Continuous ECG and BP recordings were obtained during supine rest, sitting, controlled respiration (12 breaths/min), standing, exercise at heart rates of 100 and 130 beats/min, and after 5 and 15 minutes of seated recovery. No differences were observed between A and C in the vagal or high frequency (HF) components (48.0(4.0) vs 44.2(6.9) nu), in the low frequency (LF) components (55.8(6.9) vs 52.0(4.0) nu), or in the LF/HF ratios (1.72(0.4) vs 1.22(0.2)) of the HRV spectral components at rest or other experimental conditions, despite the lower resting heart rates of the A (53.1(1.8) vs 65.1(2.1) beats/min; p $<$ 0.05). Standing and exercise decreased the HF components and increased the LF/HF ratios similarily in both the A and C, controlled respiration induced similar rises in the HF component of HRV. Despite a significantly higher systolic BP in athletes, no difference was observed between A and C in the HF or LF components of either systolic or diastolic BPV. Exercise induced an increase in the HF component of BPV which was associated with the rise in breathing frequency. These results indicate a similar sinoatrial sympathovagal balance in A and C suggesting that training-induced bradycardia could result from an adaptation in the intrinsic sinoatrial properties. Also, endurance training does not appear to influence the beat-to-beat BPV.