Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 109-124).

Aging is associated with increases in regional and systemic vascular resistance and impaired ability to increase blood flow to active muscles during exercise. Aging enhances vasoconstrictor responsiveness in both humans and animals, and an increase in Angiotensin II-induced vasoconstriction is one possible mechanism for old age-associated increase in muscle vascular resistance. The purpose of this study was to determine 1) whether aging alters Ang II-induced vasoconstriction, 2) whether exercise training attenuates the age-associated alteration in Ang II-mediated vasoconstriction, and 3) the mechanism(s) through which aging and exercise training alter Ang II-induced vasoconstriction in rat skeletal muscle arterioles. Male Fischer 344 rats were assigned to 4 groups: Young sedentary (YS; 4 months), old sedentary (OS; 24 months), young trained (YT) and old trained (OT). Exercise-trained groups performed treadmill exercises for 60 min/day at 15 m/min, on a 15º incline for 5 days/week for 10-12 weeks. First-order (1A) arterioles were isolated from soleus and gastrocnemius muscles for in vitro experimentation. Intraluminal diameter changes were determined in response to the cumulative addition of Ang II (3×10-11 - 3×10-5 M). Ang II dose responses were then determined following the removal of endothelium and treatment with NG-nitro-L-arginine methyl ester (L-NAME, 10-5 M), a nitric oxide synthase (NOS) inhibitor. Ang II-induced vasoconstriction was augmented in the aged skeletal muscle arterioles, both in soleus and gastrocnemius muscles, and age-associated increases in Ang II-induced vasoconstriction were abolished with the removal of endothelium and with L-NAME. Exercise training ameliorated the age-induced increase in Ang II-vasoconstriction, and this alteration was eliminated by the removal of endothelium and with NOS inhibition. These findings suggest that aging enhances Ang II-induced vasoconstrictor responses in the arterioles from both soleus, high oxidative, and white portion of gastrocnemius, low oxidative glycolytic muscles, and this age-associated change occurs through an endothelium-dependent NOS signaling pathway. These results also demonstrated that exercise training can ameliorate the age-associated increase in Ang II vasoconstriction in the arterioles from both high oxidative and low oxidative glycolytic muscles through an endothelium-mediated NOS mechanism.

No description available.

Elevated circulating Ang II activates neurons in the forebrain cardiovascular regulatory areas to cause sympatho-excitation and hypertension. We hypothesized that circulating Ang II causes neuronal activation in the SFO and thereby activates efferent pathways to the PVN, and chronically causes activation of aldosterone production in magnocellular neurons in PVN and SON, which amplifies neuronal activation in the PVN and central sympatho-excitatory pathways. The aim of the present study was to determine the pattern of neuronal activation in forebrain nuclei by circulating Ang II and to elucidate where in the hypothalamus Ang II may stimulate aldosterone biosynthesis. Dose related effects of circulating Ang II on BP were first assessed. Wistar rats instrumented with telemetry probes were infused subcutaneously with Ang II 150 and 500 ng/kg/min for 14 days. The subcutaneous infusion of Ang II at 150 ng/kg/min increased blood pressure gradually up to 20 mmHg and at 500 ng/kg/min up to 60 mmHg. Ang II at 500 ng/kg/min increased plasma Ang II by 4-fold. To assess effects of circulating Ang II on CNS pathways, Wistar rats were implanted subcutaneously with minipumps infusing 150 and 500 ng/kg/min Ang II for 1, 4 and 14 days. Three patterns of neuronal activation were observed by sc infusion of Ang II. The SFO was activated during the first day and remained activated for 4 days, but at 14 days showed diminished activation. MnPO did not show significant activation during the first day but, after several days the activation was high and then less by 14 days. Parvocellular PVN (pPVN), magnocellular PVN (mPVN) and SON showed an initial activation that increased over time. Chronic intracerebroventricular infusion of an aldosterone synthase inhibitor or a mineralocorticoid receptor (MR) blocker attenuated the increase in Fra expression in PVN but not SON, and prevented the decrease in SFO after 14 days infusion of Ang II. A significant increase in mRNA expression of steroidogenic acute regulatory protein (StAR), a rate limiting enzyme in aldosterone production was found in glia cells of PVN and SFO assessed by rt-PCR after 3 days subcutaneous infusion of Ang II at 500 ng/kg/min. Total expression of aldosterone synthase (CYP11B2) mRNA was increased in SFO, MnPO, SON and PVN after 3 days of infusion of Ang II. After 14 days no significant changes were observed in the expression of StAR or CYP11B2 mRNA. In comparison, in adrenal StAR mRNA expression increased after 3 days but no longer after 14 days. In contrast, CYP11B2 mRNA expression in adrenal increased after both 3 and 14 days of infusion. These findings may support our hypothesis that chronic elevation of circulating Ang II increases neuronal activity in CVOs, presumably leading to activation of the PVN and SON to induce an increase in aldosterone production in magnocelular PVN and SON. In the second phase activation of CVOs appears to diminish, but an aldosterone-dependent amplifying mechanisms, causes sustained activation of the PVN and thereby hypertension.

Angiotensin II (Ang II) plays a very important role in regulating cardiac and vascular contraction and proliferation/hypertrophy via stimulation of AT1 receptors. A few studies have demonstrated that 5-lipoxygenase (5-LO) derived cysteinyl leukotrienes (CysLT) contribute to Ang II evoked tension responses in rat aortic rings. Whether CysLT would contribute to Ang II evoked Ca2+ mobilization in neonatal rat cardiomyocytes (NRC) and rat aortic smooth muscle cells (ASMC) has not been investigated. In the present study, using primary cultures of NRC and minimally passaged cultures of rat ASMC, an effort was made to address this key issue. The agonists evoked increase in cytosolic free calcium ([Ca2+]i) level was determined by fura-2 fluorescence measurement in NRC and ASMC. Total CysLT levels in the culture medium were determined using an ELISA kit. CysLT1/CysLT2 receptor mRNA levels of NRC and ASMC were quantified by Northern blot analysis. In NRC, the AT1 but not the AT2 selective antagonist, attenuated the elevations in [Ca2+]i and CysLT levels evoked by Ang II. Vasopressin (AVP) and endothelin-1 (ET-1) increased [Ca2+]i but not CysLT levels. The 5-LO inhibitor, AA861, and the CysLT1 selective antagonist, MK-571, reduced the maximal [Ca2+]i responses (Emax) to Ang II but not to AVP and ET-1. While CysLT1 antagonist reduced the Emax to leukotriene D4, (LTD4), the dual CysLT1/CysLT2 antagonist, BAY u9773, completely blocked the [Ca2+]i elevation to both LTD4 and leukotriene C4 (LTC4). Both CysLT1 and CysLT2 mRNA were detected in NRC. The inositol 1,4,5 triphosphate (InsP3) antagonist, 2-aminoethoxyphenyl borate (2-APB), attenuated the [Ca2+]i responses to Ang II and LTD4. In ASMC, Ang II, ET-1 and AVP evoked [Ca2+]i responses were significantly higher in the cultured ASMC isolated from spontaneously hypertensive rats (SHR) compared to ASMC derived from age-matched normotensive Wistar-Kyoto (WKY) strain. Addition of either MK571 or BAY u9773, reduced the Emax values to Ang II (but not to ET-1and AVP) in both strains. While BAY u9773 abolished the [Ca2+]i responses evoked by both LTD4 and LTC4, MK571, the CysLT1 antagonist reduced the responses evoked by LTD4 but not LTC4. The basal CysLT levels were higher in the ASMC of SHR. Ang II but not ET-1 and AVP evoked time and concentration dependent increases in CysLT levels in ASMC of both WKY and SHR strains. The AT1 selective antagonist, losartan, but not the AT2 antagonist, PD123319, attenuated the increases in [Ca2+]i and CysLT levels evoked by Ang II. The InsP3 antagonist, attenuated the [Ca2+]i responses to Ang II, LTD4 and LTC4. Both CysLT1 and CysLT2 mRNA were detected in the ASMC of either strain; but they were significantly higher in SHR. These data suggest that AT1 mediated CysLT production contributes to Ang II evoked Ca2+ mobilization in NRC and that elevated CysLT production along with increased expression of both CysLT1/CysLT2 receptors may account for the exaggerated [Ca2+]i responses to Ang II in ASMC of SHR due to enhanced mobilization of Ca2+ from InsP3 sensitive intracellular Ca2+ stores.

In large molecular systems such as DNA, supramolecular complexes and dendrimers, functional groups located at different parts of the molecular structure can act as charge donors or acceptors, and photoinduced intramolecular charge transfer can occur. An analogous scenario can be found in colloidal semiconductor nanocrystals, most evident in type-II heterostructures, where the relative band-alignment of the constituent materials are in a stagger configuration. Such a configuration, provides an energetically favourable situation for an photo-generated electron to be transferred from one material to the other, confining the electron and the hole in different domains of the nanostructure. A less obvious scenario in nanocrystals is when the core is thought of as the donor group, and the surface as the acceptor group. In such a scenario, the localization of electron or hole at surface defect sites, a process that occurs in every nanocrystal, can be thought of as an ``intramolecular" charge transfer. The studies presented in this dissertation are an attempt to further understand charge transfer processes in semiconductor nanostructures, in particular, those occurring within the same nanocrystals. This is carried out by a combination of spectroscopic techniques and modelling. First, time-resolved fluorescence measurements are used to investigated surface trapping/de-trapping dynamics in CdSe and CdSe/CdS/ZnS core/shell/shell quantum dots. A kinetic model, in which trapping/de-trapping is described with Marcus' classical electron transfer theory, is used to analyzed our results, yielding excellent agreement between model and experiment. Second, the influence of temperature and solvent environment in the optical spectra of CdSe/CdTe nanorods are examined. Solvatochromic shifts in these heterostructures are found to be larger than those observed in core-only quantum dots. Finally, ultrafast dynamics and biexciton states in CdSe/CdTe quantum dots are probed using two-dimensional optical spectroscopy. The fine structure of the lowest exciton and biexciton states are calculated for a model system with type-II band-alignment and simulations of 2D spectra are performed.

Adding to a growing body of research on women and religion in English Canada, this historical study offers a glimpse inside convent culture in 1950s and ’60s Ontario, an area seldom studied by Canadian historians. The oral histories of two teaching communities in the Diocese of London, Ontario - the Ursuline Sisters of the Chatham Union and the Ontario Province of the Sisters of the Holy Names of Jesus and Mary - as well as textual records from their convent archives, form the basis of this study. This thesis seeks to examine both the external and internal factors which precipitated reforms to convent life during the 1950s and 1960s, that is, the years preceding and immediately surrounding the Second Vatican Council of the Roman Catholic Church. The external factors on reform include the pre-conciliar and conciliar mandates of the institutional Church, as well as social factors such as educational reform and changes in the roles of women throughout the postwar period. The more internal factors affecting change include shifts in sisters’ communal and individual identities and changes in spirituality. Taken together, these catalysts of change are reflective of the interplay of religious belief, institutional power and gender in postwar Canadian Roman Catholicism. Analyses of Church mandates, community responses, convent discourses on girls and women, and the spiritual reading practices of sisters throughout this period of significant change reveal that the reform efforts of religious communities were not only official and prescribed, but were also unofficial and grassroots in nature.

In large molecular systems such as DNA, supramolecular complexes and dendrimers, functional groups located at different parts of the molecular structure can act as charge donors or acceptors, and photoinduced intramolecular charge transfer can occur. An analogous scenario can be found in colloidal semiconductor nanocrystals, most evident in type-II heterostructures, where the relative band-alignment of the constituent materials are in a stagger configuration. Such a configuration, provides an energetically favourable situation for an photo-generated electron to be transferred from one material to the other, confining the electron and the hole in different domains of the nanostructure. A less obvious scenario in nanocrystals is when the core is thought of as the donor group, and the surface as the acceptor group. In such a scenario, the localization of electron or hole at surface defect sites, a process that occurs in every nanocrystal, can be thought of as an ``intramolecular" charge transfer. The studies presented in this dissertation are an attempt to further understand charge transfer processes in semiconductor nanostructures, in particular, those occurring within the same nanocrystals. This is carried out by a combination of spectroscopic techniques and modelling. First, time-resolved fluorescence measurements are used to investigated surface trapping/de-trapping dynamics in CdSe and CdSe/CdS/ZnS core/shell/shell quantum dots. A kinetic model, in which trapping/de-trapping is described with Marcus' classical electron transfer theory, is used to analyzed our results, yielding excellent agreement between model and experiment. Second, the influence of temperature and solvent environment in the optical spectra of CdSe/CdTe nanorods are examined. Solvatochromic shifts in these heterostructures are found to be larger than those observed in core-only quantum dots. Finally, ultrafast dynamics and biexciton states in CdSe/CdTe quantum dots are probed using two-dimensional optical spectroscopy. The fine structure of the lowest exciton and biexciton states are calculated for a model system with type-II band-alignment and simulations of 2D spectra are performed.

Elevated circulating Ang II activates neurons in the forebrain cardiovascular regulatory areas to cause sympatho-excitation and hypertension. We hypothesized that circulating Ang II causes neuronal activation in the SFO and thereby activates efferent pathways to the PVN, and chronically causes activation of aldosterone production in magnocellular neurons in PVN and SON, which amplifies neuronal activation in the PVN and central sympatho-excitatory pathways. The aim of the present study was to determine the pattern of neuronal activation in forebrain nuclei by circulating Ang II and to elucidate where in the hypothalamus Ang II may stimulate aldosterone biosynthesis. Dose related effects of circulating Ang II on BP were first assessed. Wistar rats instrumented with telemetry probes were infused subcutaneously with Ang II 150 and 500 ng/kg/min for 14 days. The subcutaneous infusion of Ang II at 150 ng/kg/min increased blood pressure gradually up to 20 mmHg and at 500 ng/kg/min up to 60 mmHg. Ang II at 500 ng/kg/min increased plasma Ang II by 4-fold. To assess effects of circulating Ang II on CNS pathways, Wistar rats were implanted subcutaneously with minipumps infusing 150 and 500 ng/kg/min Ang II for 1, 4 and 14 days. Three patterns of neuronal activation were observed by sc infusion of Ang II. The SFO was activated during the first day and remained activated for 4 days, but at 14 days showed diminished activation. MnPO did not show significant activation during the first day but, after several days the activation was high and then less by 14 days. Parvocellular PVN (pPVN), magnocellular PVN (mPVN) and SON showed an initial activation that increased over time. Chronic intracerebroventricular infusion of an aldosterone synthase inhibitor or a mineralocorticoid receptor (MR) blocker attenuated the increase in Fra expression in PVN but not SON, and prevented the decrease in SFO after 14 days infusion of Ang II. A significant increase in mRNA expression of steroidogenic acute regulatory protein (StAR), a rate limiting enzyme in aldosterone production was found in glia cells of PVN and SFO assessed by rt-PCR after 3 days subcutaneous infusion of Ang II at 500 ng/kg/min. Total expression of aldosterone synthase (CYP11B2) mRNA was increased in SFO, MnPO, SON and PVN after 3 days of infusion of Ang II. After 14 days no significant changes were observed in the expression of StAR or CYP11B2 mRNA. In comparison, in adrenal StAR mRNA expression increased after 3 days but no longer after 14 days. In contrast, CYP11B2 mRNA expression in adrenal increased after both 3 and 14 days of infusion. These findings may support our hypothesis that chronic elevation of circulating Ang II increases neuronal activity in CVOs, presumably leading to activation of the PVN and SON to induce an increase in aldosterone production in magnocelular PVN and SON. In the second phase activation of CVOs appears to diminish, but an aldosterone-dependent amplifying mechanisms, causes sustained activation of the PVN and thereby hypertension.

Las apolipoproteínas más abundantes de HDL son la apoA-I y la apoA-II. La concentración plasmática de apoA-I está inversamente relacionada con el riesgo de enfermedad coronaria y su papel en las HDL es bien conocido. La apoA-I tiene un papel estructural muy importante en HDL, interacciona con receptores de HDL provocando el eflujo de colesterol de membranas celulares y es cofactor de la LCAT. En cambio, el papel que juega la apoA-II en el metabolismo lipoproteico y en el desarrollo de la arteriosclerosis es menos conocido. La línea de ratones transgénicos con más expresión de apoA-II humana (línea 11.1) alimentada con dieta aterogénica desarrolla hiperlipemia combinada, deficiencia de HDL y aumento notable de susceptibilidad a la arteriosclerosis. Los ratones transgénicos de apoA-II humana de la línea 11.1 presentaron un gran aumento del área de tinción para epítopos derivados de oxidación en estas lesiones respecto de los controles. En el estudio de las propiedades antioxidantes de las HDL de los ratones 11.1, éstas presentaron una menor capacidad de protección frente a la oxidación de lipoproteínas con apoB, que las HDL de ratones controles y que los transgénicos 25.3 (baja expresión de apoA-II). Las HDL de los ratones transgénicos 11.1 presentaron una composición alterada con gran cantidad de apoA-II humana, y disminución de apoA-I, PON1 y PAF-AH, que probablemente explican la menor protección frente a la oxidación que proveen estas HDL. Estos cambios en las partículas de HDL no son debidos a cambios en la transcripción de los genes de apoA-I, PON1, PAF-AH, LCAT. Sin embargo, en ensayos in vitro se comprobó que la apoA-II humana es capaz de desplazar la PON1 de la partícula de HDL. La alteración en la capacidad antioxidante de las HDL de transgénicos 11.1 explica, al menos en parte, la susceptibilidad a la arteriosclerosis aumentada en estos animales en dieta aterogénica. En el estudio de la capacidad de estas HDL de realizar transporte reverso de colesterol, los resultados mostraron que, a pesar de la deficiencia parcial de HDL que presentan, los ratones transgénicos 11.1 no mostraron una alteración importante en el ritmo de transporte reverso de colesterol específico de macrófagos, respecto de los ratones controles. Así pues, la susceptibilidad a la arteriosclerosis en ratones transgénicos 11.1 alimentados con dieta aterogénica, no parece ser atribuible a una disminución del transporte reverso de colesterol específico de macrófagos. / ApoA-I and apoA-II are the most abundant apolipoprotein in HDL. ApoA-I plasma concentration is inversely related to coronary artery disease risk and its role in HDL is well known. ApoA-I has a very important structural role in HDL, it binds to HDL receptors triggering cholesterol efflux from cell membranes and is LCAT cofactor. However, the role of apoA-II in lipoprotein metabolism and atherosclerosis development is less known.The high expressor human apoA-II transgenic mice (line 11.1) challenged with atherogenic diet develops combined hiperlipidemia, HDL deficiency and high atherosclerosis susceptibility. Line 11.1 mice showed a dramatic increase in staining area for oxidation-derived epitopes in aortic lesions, compared to control mice. HDL from 11.1 line presented impaired ability to protect apoB lipoprotein against oxidation when compared to control and 25.3 mouse line (low human apoA-II expressor). HDL from 11.1 mice showed an altered composition with high quantities of human apoA-II, low apoA-I, PON1 and PAF-AH, that likely accounts for the impaired protection against oxidation found in these mice. However, these changes are not due to changes in transcription of apoA-I, PON1, PAF-AH or LCAT genes. On the other hand, human apoA-II is able to displace PON1 from the HDL particle, as shown by in vitro assays. Impairment of antioxidant ability of HDL from 11.1 transgenic mice could explain, at least in part, the enhanced atherosclerosis susceptibility found in these animals in atherogenic diet.In the study of the ability of HDL from 11.1 transgenic mice to carry out reverse cholesterol transport, the results showed that, despite their HDL deficiency, 11.1 transgenic mice did not presented an altered flux in macrophage-specific reverse cholesterol transport. Therefore, the enhanced atherosclerosis susceptibility of 11.1 transgenic mice does not seem attributable to an impaired macrophage-specific reverse cholesterol transport.