Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xi, 87 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 71-79).

Thesis (Ph. D.)--University of Missouri--Columbia, 1999. / "July 1999." Typescript. Vita. Includes bibliographical references (leaves 151-174). Also available on the Internet.

abstract: Birds have plasma glucose levels that are 1.5-2 times greater than mammals of similar body mass in addition to higher free fatty acid concentrations, both of which would typically impair endothelium-dependent vasodilation if observed in mammals. Endothelium-dependent vasodilation can be stimulated in mammals through the use of acetylcholine (ACh), which primarily acts through nitric oxide (NO) and cyclooxygenase (COX)-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors (EDHFs). Very few studies have been conducted on small resistance systemic arteries from birds. The hypothesis was that because birds have naturally high glucose and free fatty acid concentrations, ACh-induced vasodilation of isolated arteries from mourning doves (Zenaida macroura) would be independent of endothelial-derived factors and resistant to high glucose-mediated vascular dysfunction. Small resistance mesenteric and cranial tibial (c. tibial) arteries were pre-constricted to 50% of resting inner diameter with phenyleprine then exposed to increasing doses of ACh (10-9 to 10-5 μM) or the NO donor, sodium nitroprusside (SNP; 10-12 to 10-3 μM). For both vessel beds, ACh-induced vasodilation occurred mainly through the activation of potassium channels, whereas vasodilation of mesenteric arteries additionally occurred through COX. Although arteries from both vessel beds fully dilated with exposure to sodium nitroprusside, ACh-mediated vasodilation was independent of NO. To examine the effect of high glucose on endothelium-dependent vasodilation, ACh dose response curves were conducted following exposure of isolated c. tibial arteries to either a control solution (20mM glucose) or high glucose (30mM). ACh-induced vasodilation was significantly impaired (p = 0.013) when exposed to high glucose, but normalized in subsequent vessels with pre-exposure to the superoxide dismutase mimetic tiron (10 mM). Superoxide concentrations were likewise significantly increased (p = 0.0072) following exposure to high glucose. These findings indicate that dove arteries do not appear to have endogenous mechanisms to counteract the deleterious effects of oxidative stress. Additional studies are required to assess whether endogenous mechanisms exist to protect avian vascular reactivity from systemic hyperglycemia. / Dissertation/Thesis / M.S. Nutrition 2012

xvii, 174 p. : ill. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / During acute altitude exposure, humans maintain higher skin temperature and lower core body temperature. However, the role of cutaneous vascular regulation in these thermoregulatory differences is unclear. Therefore, the purpose of these studies was to investigate the impact of altitude exposure on reflex control of skin blood flow and core temperature during cold exposure. In Chapter IV, the effects of hypoxia and hypocapnia on cutaneous vasoconstriction during mild cold exposure were investigated. We found that hypoxia stimulates cutaneous vasodilation in men whereas skin blood flow is unaltered in women. However, during whole body cooling skin blood flow is upward shifted in both sexes. The development of hypocapnia does not affect the vascular response to hypoxia in either sex, but reduces the magnitude of cutaneous vasoconstriction during cold exposure by 50% in women. In Chapter V, we studied the timecourse of α-adrenergic blockade by yohimbine in the cutaneous circulation and how the duration of cold exposure modulates cotransmitter-mediated vasoconstriction during cold stress. We found that yohimbine produces functional α-adrenergic blockade within 30 minutes of initial delivery and completely abolishes reflex cutaneous vasoconstriction during mild cold stress. This latter finding was surprising, and an additional protocol demonstrated that cotransmitter-mediated vasoconstriction only participates in the vascular response to cold stress when the exposure is more prolonged. In Chapter VI, the effects of hypoxia on cutaneous vasoconstrictor mechanisms and core cooling rate were tested during more prolonged and severe cold stress. In contrast to our findings during brief cold exposure, we showed that cutaneous vasoconstriction during prolonged cold stress is potentiated by hypoxia and abolishes hypoxic vasodilation. Moreover, increased cotransmitter-mediated vasoconstriction appears to account for this response. Hypoxia had no effect on core cooling rate during severe cold exposure. The selective potentiation of cotransmitter-mediated vasoconstriction observed during hypoxia in Chapter VI provided the basis for Chapter VII. This study was designed to test the effect of hypoxia on cutaneous vascular responsiveness to peripherally stimulated sympathetic vasoconstriction. The results demonstrated that α-adrenergic vasoconstrictor transduction is not affected by hypoxia, and that stimulation of adrenergic nerves with tyramine does not elicit cotransmitter-mediated vasoconstriction in skin. / Adviser: John R. Halliwill

Orientadores: Fernanda Klein Marcondes, Pedro Duarte Novaes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-16T16:16:47Z (GMT). No. of bitstreams: 1 Guzzoni_Vinicius_M.pdf: 984751 bytes, checksum: ee30bc1a29a47fa0be69646bf0ecf92f (MD5) Previous issue date: 2010 / Resumo: Os riscos à saúde decorrentes do consumo de esteróides anabólicos androgênicos constituem um problema de saúde pública. Em estudo anterior desenvolvido por nosso grupo de pesquisa, foi observado que o decanoato de nandrolona cancelou os efeitos vasculares adaptativos promovidos pelo treinamento físico resistido, em aorta torácica de ratos, sugerindo uma ação inibitória sobre a síntese de óxido nítrico. Visando elucidar os mecanismos envolvidos nestes efeitos, os objetivos do presente estudo foram: analisar a sensibilidade in vitro da aorta torácica ao efeito vasodilatador da acetilcolina (ACh), a espessura da parede vascular, a concentração tecidual de óxido nítrico (NO) e espécies reativas de oxigênio (EROx), em aorta torácica isolada de ratos Wistar divididos em 4 grupos experimentais: não-treinado + veículo; treinado + veículo; não-treinado + nandrolona; treinado + nandrolona. Após o período de adaptação, o treinamento físico resistido consistiu de sessões de saltos em meio líquido com sobrecarga de peso (4 séries, 10 repetições, 50-70% peso corporal, 5 dias por semana, 6 semanas). Dois dias após a última sessão de treinamento, os animais foram sacrificados por decapitação e a aorta torácica foi isolada para a obtenção de três anéis, os quais foram utilizados para obtenção da curva concentração-efeito à ACh in vitro, avaliação in vitro da produção de óxido nítrico (ON) e de espécies reativas de oxigênio (EROx), e para análise da espessura da camada média. Os dados foram analisados por ANOVA bifatorial seguido por Tukey considerando como nível de significância 5%. Animais treinados apresentaram aumento significativo na espessura da camada média da aorta torácica em relação aos respectivos grupos não-treinados. Anéis aórticos de ratos não treinados tratados com veículo ou nandrolona apresentaram relaxamento de 100% em resposta à ACh, enquanto em anéis isolados de ratos treinados tratados com veículo e nandrolona observou-se relaxamento de 79 e 51%, respectivamente. A aorta torácica de ratos treinados apresentaram menor produção de ON em relação a ratos não-treinados. A aorta isolada de ratos tratados com anabolizante apresentaram menor produção de ACh em relação ao tecido de ratos tratados com veículo. O treinamento reduziu a produção de EROx na aorta torácica de animais treinados tratados com veículo, em relação ao grupo não treinado, sem alteração em animais tratados com nandrolona. Os dados obtidos indicam que altas doses de nandrolona induziram disfunção endotelial em ratos submetidos a treinamento físico resistido. / Abstract: The risk-benefit of androgenic-anabolic steroid abuse in elite athletes has been of great corcern for researchers. Nandrolone decanoate was previously observed to inhibit the adaptative vascular effects in the thoracic aorta of rats under resistance training, probably due to an inhibitory effect on the nitric oxide synthesis. The aim of this in vitro study was to analyze the thoracic aorta sensibility to acetylcholine vasodilator effect, considering the vascular media layer thickness, the bioavailability of nitric oxide (NO) and the superoxide anion production in the thoracic aorta in Male Wistar rats, aged 2 months. Animals were assigned to four groups: non-trained animals treated with vehicle (NTV); non-trained animals treated with nandrolone (NTN); trained animals treated with vehicle (TV); and trained animals treated with nandrolone (TN). After the adaptation period, animals were submitted to resistance physical training consisting of jumps in liquid ambient with overload (4 sets, 10 repetitions, 30 second rest, 50-70% body weight-load, 5 days/week, 6 weeks). Two days after the last training session, the animals were killed by decapitation and the thoracic aorta was isolated. Thoracic aorta was divided into three parts and rings were removed from the middle third of the aorta of each animal to obtain concentration-effect curves for acetylcholine (ACh). Segments obtained from the part below the middle third were processed to evaluate the production of nitric oxide (NO) and oxygen reactive species (EROx). Data were analyzed using 2-way analysis of variance (ANOVA) followed by Tukey test, at a 5% significance level. A significant increase in the final body weight was observed in the four experimental groups, while a significant decrease was found in the final body weight for the groups treated with nandrolone. Trained animals showed a significant increase in the aorta middle layer thickness compared to non-trained groups. Aortas of the rats treated with nandrolone showed a decrease in vasodilator response compared to those of rats treated with vehicle. Isolated rings of non-trained rats treated with vehicle or nandrolone revealed 100% relaxation in response to ACh, while isolated rings of the trained rats treated with vehicle and nandrolone showed relaxation of 79 and 51%, respectively. Animals treated with nandrolone presented decreased production of NO compared to those treated with vehicle. The EROx production dropped in trained rats treated with vehicle but not in those treated with nandrolone. In conclusion, the physical training protocol used in this study caused morphological, functional, and metabolic adaptations in the aorta of the rats; supraphysiological doses of nandrolone potentiated and inhibited the responses triggered by intense physical training. / Mestrado / Fisiologia Oral / Mestre em Odontologia

Effects of neurokinin A (NKA) and substance P (SP) on coronary resistance vessels were studied in isolated guinea pig hearts perfused with isotonic buffer containing 20 mM KCl. Injections of NKA and SP caused dose-dependent reductions in perfusion pressure with ED50 values of 14.0 and 0.326 pmol, respectively. Blockade of nitric oxide synthesis or removal of the endothelium inhibited vasodilator responses to neurokinins. Infusions of NKA or SP caused tachyphylaxis and cross-desensitization to the other neurokinin but not to acetylcholine. Injections of 2.5 nmol NKA increased perfusion pressure by 31 ± 8% when given after tachyphylaxis developed to infused SP (2.5 nmol/100 μl/min). It was concluded that 1) neurokinins cause an endothelium-dependent relaxation of coronary resistance vessels by stimulating NK-1 receptors on endothelial cells, and 2) desensitization of the receptor mediating vasodilation unmasks a vasoconstrictor response to NKA.

OBJECTIVE - Exercise training has been shown to restore vasodilation to nitric oxide synthase (NOS) activation in arterioles distal to coronary artery occlusion. Because reactive oxygen species are generated during NOS uncoupling and the production of vasodilator H2O2 is increased during exercise in patients with coronary disease, we proposed that H2O2 may contribute to the restoration of vasodilation in porcine coronary occlusion model. METHODS AND RESULTS - Left circumflex (LCX) coronary artery of miniature swine was progressively occluded for 8 weeks followed by exercise training (EX; 5 days/wk treadmill) or sedentary (SED) protocols for 12 weeks. Arterioles were isolated from distal LCX and nonoccluded left anterior descending (LAD) artery for in vitro study. Vasodilation to NOS activators adenosine and ionomycin was impaired in SED LCX, but not LAD, arterioles. This impairment was restored by L-arginine. NO production induced by adenosine was also reduced in SED LCX arterioles. EX had no effect on LAD arterioles but improved NO production and restored dilation of LCX arterioles. NOS blockade (L-NAME) inhibited vasodilation to NOS activators in LAD (SED & EX) arterioles but was ineffective in SED LCX arterioles. In EX LCX arterioles, vasodilation to NOS activators was slightly inhibited by L-NAME but abolished by catalase. H2O2 production was markedly increased by adenosine in EX LCX arterioles. CONCLUSIONS - This study demonstrates that endothelium-dependent NO-mediated dilation is impaired in SED LCX arterioles and that EX training restores the impaired function. It appears that H2O2, in addition to NO, contributes significantly to EX-induced restoration of endothelium-dependent dilation of coronary arterioles distal to occlusion.

Peripheral arterial occlusive disease (PAOD) is an ischemic disease characterized by narrowing of the peripheral arteries due to the accumulation of atherosclerotic plaque in the inner lining of the vessels, which disrupts blood flow to downstream tissues. Blood can be redirected into collateral vessels, natural bypasses around arterial occlusions, causing shear-induced outward remodeling of the vessels. The enlarged vessels facilitate transfer of increased blood flow to downstream tissues. The remodeling process, however, may impair vasodilation, which in turn may cause or contribute to intermittent claudication- transient pain brought on by locomotion. To stimulate the growth of collateral arteries, the femoral arteries of young, otherwise healthy mice were ligated distally to the profunda femoris, the stem to the gracilis collateral circuit. The diameter of the profunda femoris artery was measured at rest and following gracilis muscle contraction 7 and 28 days post-surgery using intravital microscopy. Enlarged resting diameter, consistent with collateral enlargement, and impaired vasodilation was observed at day 7, but not at day 28. To determine if impaired functional vasodilation is due to impaired endothelial- or smooth muscle-dependent responses during outward remodeling, cell-dependent vasodilators were applied to the hindlimb. Endothelial- and smooth muscle-dependent vasodilation was significantly impaired 7 days post-ligation, but not 28 days after. This data supports the hypothesis that smooth muscle dysfunction causes impaired functional vasodilation in the early stages of collateral enlargement.

Functional hyperemia and arteriolar vasodilation are impaired with chronic ischemia. We sought to examine the impact of chronic ischemia on collateral artery function. For this we used two hindlimb ischemia models to dissect the impact of different repair processes on collateral function. Ligation of the femoral artery increases shear stress in the muscular branch and results in outward remodeling and arteriogenesis. In contrast, resection of the femoral artery proximal to the muscular branch induces blood flow divergence and neutral remodeling along with expectedly greater hypoxia and inflammation. On day 14 after each surgery the diameter of the muscular branch was measured using sidestream dark field (SDF) imaging before and after gracilis muscle stimulation. A slight, but not statistically significant, impairment in functional vasodilation was observed in ligated mice (69±10% average diameter increase compared to 74±7% average diameter increase). Resected mice exhibited slightly (not statistically significant) enhanced collateral artery functional vasodilation (104±16% average diameter increase) but were also refractory to the restoration of resting vascular tone following the cessation of stimulation. Outward remodeling did not significantly impair vascular function, whereas neutral remodeling and tissue hypoxia induced impaired vascular tone.

A disfunção endotelial atua tanto na aterogênese como na precipitação das síndromes coronárias agudas. A redução da biodisponibilidadedo óxido nítrico é expressão de endotélio disfuncional. O mecanismo desta redução não está elucidado. A presença de disfunção endotelialfoi correlacionada com fatores de risco (FR), nitrato sanguíneo e fatores genéticos (polimorfismo da óxido nítrico sintase endotelial, fibrinogênio e PAI-1) em um grupo de 128 pacientes com infarto do miocárdio (IAM) e idade = 40 anos, submetidos a ultra-som de artéria braquial. Os resultados foram comparados com um grupo jovens saudáveis. Verificou-se que pacientes jovens com IAM apresentavam disfunção endotelial em associação com FR, alterações bioquímicas e níveis aumentados de nitrato, porém sem alterações genéticas / The endothelial dysfunction plays an important roll in the atherogenesis and precipitation of acute coronary syndromes. The reduction of bioavailability of the nitric oxide is the expression of endothelial dysfunction. The exact mechanism of this reduction is not yet well explained. In order to evaluate the presence of endothelial dysfunction and correlation with risk factors (FR), nitrate blood levels and genetic factors (endothelial nitric oxide synthease polymorphism, fibrinogen and PAI-1) a 128 myocardial infarction patients group with age = 40 year was studied, and underwent a brachial artery ultra-sound. The results were compared with a group of young health individuals. The study found that the young patients with myocardial infarctions showed endothelial dysfunction with associated risks factors, biochemical changes and higher levels of nitrate, although without any significant genetic changes