Browsing by Subject "Endothelium"

Now showing 1 - 3 of 3
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    Brachial Artery Response to Reactive Hyperemia: Describing High-Flow-Mediated Constriction in Healthy Children, Adolescents and Adults, and the Intra- and Inter-day Reproducibility of High-Flow-Mediated Constriction Response in Adults
    (2016-07) Ostrem, Joseph
    Endothelial dysfunction has been shown to be an important precursor in the atherosclerotic process. A widely used, non-invasive method of assessing endothelial function is flow-mediated dilation (FMD). This method of vascular health assessment utilizes ultrasound imaging and has historically focused on the degree of vessel dilation in response to reactive hyperemia to ascertain endothelial function. The brachial artery's ideal vessel diameter and its nitric oxide-mediated response to reactive hyperemia make it the preferred site of assessment. Also, a strong correlation between endothelial function in coronary and brachial arteries has been reported, which allows brachial FMD to be a surrogate measure of coronary function. Additionally, many studies have shown impairment of FMD in response to a range of cardiovascular risk factors and has been inversely associated with future CVD events. However, a biphasic response, where vessel constriction occurs prior to dilation, has been observed during reactive hyperemia. The constriction phase during reactive hyperemia has been largely overlooked in FMD research, termed high-flow-mediated constriction (H-FMC). Therefore, the purpose of the following dissertation was to perform a cross-sectional examination of children, adolescents and adults to quantify the frequency and magnitude of H-FMC, determine potential influences of sex, age, body composition, cardiovascular and metabolic factors on H-FMC, and report the reproducibility of an H-FMC in young adults to lend further insight to the existing body of research surrounding FMD and H-FMC assessment.
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    Evaluation of gender differences in endothelium-independent dilation in healthy adults using peripheral arterial tonometry
    (2012-12) McCue, Meghan Cameron
    Peripheral arterial tonometry (PAT) is a non-invasive method used to evaluate vascular function. PAT is often used to measure digital pulsatile volume changes in response to reactive hyperemia, which provides a measure of endothelium-dependent dilation (EDD). Reactive hyperemia does not allow one to quantify endothelium-independent dilation (EID), which is typically measured using sublingual nitroglycerin (NTG) mediated dilation. Though most research examining vascular function and cardiovascular disease has focused on EDD, there is evidence that cardiovascular risk factors may impair EID. To our knowledge, PAT has not been used with NTG to determine EID. The purpose of this study was to examine the microvascular vasodilation response to nitroglycerin (NTG) in healthy adults using PAT. Microvascular responses to reactive hyperemia and NTG were evaluated in 86 (41 F, 45 M) healthy subjects (age 37±5 yrs). Beat-to-beat plethysmographic measurements of finger arterial pulse waves were recorded for 5-min following reactive hyperemia. After a 10-min rest period, sublingual NTG (0.4 mg) was administered and PAT signal changes were measured for 10-min. Peak reactive hyperemic index (RHI) and peak NTG-mediated index (NMI) were determined in all subjects. Though there were no significant gender differences in peak RHI (2.07±0.56 F vs. 1.91±0.58 M, P=0.20), peak NMI was significantly greater in females (3.11±1.59 F vs. 2.50±1.34 M, P=0.05). Time to peak NMI was not significantly different between genders (7-min, 28-s [±1-min, 47-s] M, vs. 7-min, 14-s [±1-min, 49-s] F, P=0.58). In this population of healthy adults, RHI did not differ by gender. However, we observed a significantly greater microvascular vasodilation response to NTG using PAT in females than in males. Significance of this finding is unclear, but may indicate the beginning of cardiovascular changes in adult males, as detected with lower peak NMI at the microvascular level. Future studies are needed to determine the exact mechanism underlying the reported gender differences in EID.
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    Manganese superoxide dismutase and cardiovascular aging phenotypes in mice
    (2012-09) Ross, Carolyn Marie
    Reactive oxygen species (ROS) have been implicated in the pathogenesis of a number of cardiovascular diseases. Furthermore, recent data from in vitro model systems suggests that mitochondrial ROS production may initiate a vicious cycle termed ROS-induced ROS-release (RI-RR). Whether this phenomenon occurs in vivo or is amplified by aging is not known. We hypothesized that induction of RI-RR by experimentally reducing manganese superoxide dismutase (a mitochondrial antioxidant enzyme) impairs aortic endothelial function and aortic valve function with aging, and that these functional changes would be associated with transcriptional repression of sirtuin family genes, which are known to be associated with aging and age-related diseases. For our studies, we used young (2 mo) and old (>18 mo) MnSOD wild-type (WT) and MnSOD-deficient (HET) mice. In aorta, increasing age significantly impaired vasomotor function (isolated organ chamber baths) in WT mice, but endothelial function was not further impaired in HET mice. Inhibition of NAD(P)H oxidase significantly improved endothelial function in aged WT mice. NAD(P)H oxidase inhibition in HET mice, however, paradoxically worsened endothelial function in young and old animals. Aortic valve function (echocardiography) was unaffected by aging in both WT and HET mice. Interestingly, expression of antioxidant enzymes and multiple sirtuin isoforms (quantitative real-time RT-PCR) were slightly reduced by aging in aorta, but were dramatically reduced in aortic valve. These transcriptional changes were not amplified in either aorta or aortic valve from HET mice. Collectively, our data demonstrate that the transcriptional responses and phenotypes elicited by aging and alterations in mitochondrial antioxidant capacity differ dramatically between aorta and aortic valve. We conclude that reductions in mitochondrial antioxidant capacity do not independently contribute to development of overt cardiovascular disease, and instead suggest that oxidative stress may play a modulatory role in cellular and organismal responses to pathophysiological stimuli that drive age-related cardiovascular disease.