The purpose of this study was to determine if α1- adrenergic receptor blockade alters the hemodynamic response to exercise in young (<25 yr) male adult borderline hypertensives differently than in young normotensives. Five hypertensive (HTN, MAP>105 mmHg) and 7 normotensive (NTN, MAP<95 mmHg) college-age males underwent two 30 min bouts of cycle ergometry exercise at 50% V02Pk in a warm (25°C, 50% rh) environment; one bout occurred followed α1-receptor blockade with prazosin (HTN-α, NTN-α) and the other following placebo administration (HTN-p, NTN-p). At rest, HTN-p exhibited an elevated cardiac output (Q, p=.024) and MAP (p=.007). Resting Q was similar for HTN-α and NTN-α. Resting heart rate (HR) was elevated more in HTN-α than NTNα (p=.013) and not different for placebo. Resting and exercise forearm blood flows were similar between groups and altered similarly with prazosin. Exercise resulted in greater (p=.035) Q for HTN vs NTN (HTN-u > NTN-α; HTN-p = NTN-p). HR was higher (p=.043) with prazosin for both groups. Regardless of drug treatment, MAP was stable for NTN while it declined after 10 min of exercise in HTN. Rectal temperatures rose above baseline after 10 min. since Q was similar between groups with placebo but not with α1- blockade, and FBF, MAP, and HR were similarly altered between drug trials, it was concluded that young male hypertensives have an elevated blood pressure due to an elevated Q. In this group, α1-blockade may reduce Q by reducing central venous return. / Ph. D.

Includes 4 published papers by the author as part of appendix 9 / Bibliography: leaves 1-19 (second sequence) / System requirements for accompanying computer disk: IBM-compatible computer. Other requirements: Dbase. / 1 v. (various pagings) ; / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Summary: describes and evaluates an economical method of collecting a large amount of data on thousands of patients suffering from essential hypertension and establishes the reliability of the data collected in this way. Also provides information on the tolerability and effectiveness of nifedipine / Thesis (M.D)--Dept. of Clinical and Experimental Pharmacology, University of Adelaide, 1993

M.A. (Psychology) / Please refer to full text to view abstract

D.Litt. et Phil. (Psychology) / The aim of this study was to investigate the effect that hypertension has on brain function. A neuropsychological test battery comprising of the following tests was employed as a multivariate measure of brain dysfunction in a quasiexperimental, matched group design: a) The Complex Figure Test of Rey (copy, immediate recall and delayed recall), b) the Logical Memory Test, c) the Digits Span Test, d) the Verbal Paired Associate Learning Subtest, e) the Controlled Oral Word Generation Test, fr the Trail Making Test, and the Digit Symbol Substitution Subtest, This permitted a comparison in brain functioning between a group of hypertensive and a group of normotensive participants that were matched according to age, handedness, level of education and sex. The matching of variables increased the sensitivity of the study by controlling extraneous variables and ensured that the groups were compatible on the paired variables. The results were statistically analyzed by employing the Mann-Whitney U statistic for small groups and the Chi-square statistic on the measured variables. Further, content analysis was employed to test for significant differences in strategies of coping, immediate recall and delayed recall of the Complex Figure of Rey. The results indicated that: 1. there were significant differences in attention and concentration, motor functioning, perceptual abilities, information processing, memory, and planning and organisation between the two groups, with the hypertensive group obtaininq significantly lower scores on test measuring these variables; and 2. there were no significant differences in the verbal abilities (word fluency) of the two groups. The results support previous research, finding indications of vocal lesions located across the brains of people suffering from hypertension. Practical implications of the results are discussed and recommendations for future research have been made...

M.A. / It is a well-known fact that South Africans of all races are a high risk population for the development of coronary heart disease and hypertension . More recent statistics indicate that cardiovascular disease caused 12 % of deaths amongst black South Africans in 1994 (Webster, 1996). Risk factors for CHI) can be grouped into four domains : Biomedical (e.g. hypertension, family history), behavioural (e.g. substance intake), sociodemographic (e.g. socio - economic status) and personality (e.g. Type A Behaviour). While there is a general agreement on many of the risk factors for CHIC, there are many more which are still being debated such as the influence of offspring parental heart disease and hypertension and coronary - prone behaviour. In a developing country, such as South Africa, with its heterogeneous population, it seemed that cardiovascular diseases are assuming epidemiological proportions among both White and Black South Africans, and thus appears necessary to establish whether Black patients with cardiovascular disease exhibits the TABP, closely related with diseases of the cardiovascular system among Whites. Els (1987) noted that stress associated with lifestyle changes in Black urbanisation in South Africa, not only showed psychological markers of CHD, but also physiological markers, such as substance intake. A cohort of 67 Black South African university students (38 male & 29 female), with a mean age of 23 was selected. The experimental groups being children of parents with hypertension and heart disease and the controls being children of normotensive parents and without a history of heart disease. A battery of tests were used to measure TAB, depression, hostility, anger and substance consumption. Results indicated that the experimental groups showed a significantly higher index of Type A Behaviour (p < 0, 01) than the controls and there was a significant correlation in terms of Parental hypertension and parental heart disease with coronary - prone behaviour (anger, hostility and depression) as well as substance consumption.

Indiana University-Purdue University Indianapolis (IUPUI) / Obesity increases cardiovascular disease risk and is associated with factors of the “metabolic syndrome” (MetS), a disorder including hypertension, hypercholesterolemia and/or impaired glucose tolerance. Expanding adipose and subsequent inflammation is implicated in vascular dysfunction in MetS. Perivascular adipose tissue (PVAT) surrounds virtually every artery and is capable of releasing factors that influence vascular reactivity, but the effects of PVAT in the coronary circulation are unknown. Accordingly, the goal of this investigation was to delineate mechanisms by which lean vs. MetS coronary PVAT influences vasomotor tone and the coronary PVAT proteome. We tested the hypothesis that MetS alters the functional expression and vascular contractile effects of coronary PVAT in an Ossabaw swine model of the MetS. Utilizing isometric tension measurements of coronary arteries in the absence and presence of PVAT, we revealed the vascular effects of PVAT vary according to anatomical location as coronary and mesenteric, but not subcutaneous adipose tissue augmented coronary artery contractions to KCl. Factors released from coronary PVAT increase baseline tension and potentiate constriction of isolated coronary arteries relative to the amount of adipose tissue present. The effects of coronary PVAT are elevated in the setting of MetS and occur independent of endothelial function. MetS is also associated with substantial alterations in the coronary PVAT proteome and underlying increases in vascular smooth muscle Ca2+ handling via CaV1.2 channels, H2O2-sensitive K+ channels and/or upstream mediators of these ion channels. Rho-kinase signaling participates in the increase in coronary artery contractions to PVAT in lean, but not MetS swine. These data provide novel evidence that the vascular effects of PVAT vary according to anatomic location and are influenced by the MetS phenotype.

Indiana University-Purdue University Indianapolis (IUPUI) / 17-β estradiol (E2) exerts protective effects in hypoxia-induced pulmonary hypertension (HPH) via endothelial cell estrogen receptor (ER)-dependent mechanisms. However, the effects of hypoxia on ER expression in the pulmonary-right ventricle (RV) axis remain unknown. Based on previous data suggesting a role of ER-β in mediating E2 protection, we hypothesized that hypoxia selectively up-regulates ER-β in the lung and pulmonary endothelial cells. In our Male Sprague-Dawley rat model, chronic hypoxia exposure (10% FiO2) resulted in a robust HPH phenotype associated with significant increases in ER- β but not ER-α protein in the lung via western blotting. More importantly, this hypoxia-induced ER-β increase was not replicated in the RV, left ventricle (LV) or in the liver. Hence, hypoxia-induced ER-β up-regulation appears to be lung-specific. Ex vivo, hypoxia exposure time-dependently up-regulated ER-β but not ER-α in cultured primary rat pulmonary artery endothelial cells (RPAECs) exposed to hypoxia (1% O2) for 4, 24 or 72h. Furthermore, the hypoxia induced ER-β protein abundance, while not accompanied by increases in its own transcript, was associated with ER-β nuclear translocation, suggesting increase in activity as well as post-transcriptional up-regulation of ER-β. Indeed, the requirement for ER-β activation was indicated in hypoxic ER-βKO mice where administration of E2 failed to inhibit hypoxia-induced pro-proliferative ERK1/2 signaling. Interestingly, HIF-1α accumulation was noted in lung tissue of hypoxic ER-βKO mice; consistent with previously reported negative feedback of ER-β on HIF-1α protein and transcriptional activation. In RAPECs, HIF-1 stabilization and overexpression did not replicate the effects of ER- β up-regulation seen in gas hypoxia; suggestive that HIF-1α is not sufficient for ER-β up- regulation. Similarly, HIF-1 inhibition with chetomin did not result in ER-β down-regulation. HIF-1α knockdown in RPAECs in hypoxic conditions is currently being investigated. Hypoxia increases ER- β, but not ER-α in the lung and lung vascular cells. Interpreted in context of beneficial effects of E2 on hypoxic PA and RV remodeling, our data suggest a protective role for ER-β in HPH. The mechanisms by which hypoxia increases ER-β appears to be post-transcriptional and HIF-1α independent. Elucidating hypoxia-related ER-β signaling pathways in PAECs may reveal novel therapeutic targets in HPH.

Indiana University-Purdue University Indianapolis (IUPUI) / The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.