Ribosomes are the essential machinery for cellular protein synthesis. Ribosome content is hypothesized to support muscle growth and is suggested that those with more ribosomes may better respond to resistance training. Aerobic training also elicits distinct physiological adaptations; however, no direct measures of ribosome content following aerobic training have been measured. Ribosomes interact with mitochondria for mitochondrial protein synthesis and import. Mitochondria may also provide cellular energy to ribosomes. We hypothesized that aerobic and resistance training would increase ribosome content and that ribosome content following aerobic training would correspond to changes in mitochondrial-related protein content and gene expression. Fourteen young men and women performed 6 weeks of single-legged aerobic followed by 10 weeks of bilateral resistance training. Muscle biopsies were taken following aerobic (Pre RT) and resistance training (Post RT) in the aerobically trained (EX) and control (CTL) legs. Pre RT, EX had greater COXIV staining intensity in Type 1 (1.17-fold; p=0.020) and Type 2 (1.22-fold; p=0.015) fibres compared to CTL; however, no differences in whole-muscle mitochondrial-related protein content or gene expression were observed (p>0.05). No differences in regulatory (UBF, Cyclin D1, TIF-1A, POLR-1B), cytosolic (45S, 5.8S, 18S, 28S rRNAs) or mitochondrial (12S rRNA) ribosome-related gene expression were observed (p>0.05), except for c-Myc (CTL>EX; p=0.034) and 5S rRNA (Pre RT CTL<Pre RT EX; p=0.076). When stratified for leg-lean soft tissue mass (LLSTM), legs with greater LLSTM had lower expression in 3/13 ribosome-related genes (p<0.10). When stratified for ΔLLSTM following resistance training, legs with the greatest ΔLLSTM had lower expression in 11/13 ribosome-related genes prior to (p<0.10) and less change or decrease in expression in 9/13 genes following resistance training (p<0.05). These results indicate that baseline ribosome content was sufficient to support aerobic adaptations (capillarization, VO2 peak) that were previously observed and that ribosome’s efficiency, rather than content, is likely more important to support increases in muscle hypertrophy following resistance training. / Thesis / Master of Science in Kinesiology / Ribosomes are essential in making proteins within the cell, and their content has been hypothesized to support the adaptive responses observed with exercise training. Ribosome content has previously been shown to increase following resistance training likely to support skeletal muscle growth. However as aerobic training also influences cellular adaptations, it is plausible that ribosome content also supports these training adaptations. We hypothesized that both aerobic and resistance training would increase ribosome content. Contrary to our hypotheses, no changes in ribosome content were observed following aerobic or resistance training despite previously observing adaptations characteristic of each respective training stimulus. However, those with the greatest increases in muscle mass had lower baseline ribosome content and less change in content following resistance training. These results suggest that baseline ribosome content is sufficient for aerobic adaptations and that ribosome’s efficiency is likely more important than content to elicit resistance training adaptations.

O processo inflamatório pode ser iniciado pela presença de patógenos (PAMPs) ou de moléculas associadas ao dano tecidual (DAMPs), estes sinais são reconhecidos por células do sistema imune via receptores de reconhecimento de padrão localizados na membrana ou no citoplasma destas células. A ativação da família de receptores intracitoplasmáticos do tipo NOD (NLR) pode levar à formação de complexos proteicos denominados inflamassomas, entre eles, o inflamassoma NLRP3, formado por três estruturas básicas: receptores do tipo NOD, proteína adaptadora (ASC) e pró-caspase 1. Essas caspases ativas são capazes de induzir a maturação proteolítica de interleucina-1 beta (IL-1b) e IL-18, que então são liberadas para o meio extracelular. É sabido que a hipertensão é uma doença inflamatória associada à presença de DAMPs em regiões de controle da pressão arterial, como o núcleo paraventricular do hipotálamo (PVN) bem como, que o treinamento aeróbio é uma conduta eficaz em reverter muitos dos efeitos deletérios da hipertensão. Desta forma, é nossa hipótese de trabalho que inflamassomas NLRP3 possam estar ativados na hipertensão e que o treinamento aeróbio corrija muitos déficits do controle cardiovascular por modular a resposta imune inata. Em ratos machos adultos Wistar Kyoto e ratos espontaneamente hipertensos (SHR), foram feitas análises de parâmetros cardiovasculares, além da expressão gênica dos constituintes do inflamassoma e citocinas, e proteica de citocinas no PVN de animais sedentários ou treinados por quatro semanas de ambas as linhagens. Nossos resultados mostram que animais hipertensos se caracterizam por valores aumentados de pressão arterial e frequência cardíaca de repouso, associados à disfunção autonômica ao coração e vasos. SHR apresentam inflamação no PVN, o que foi evidenciado pelo elevado perfil de expressão dos constituintes da via do inflamassoma NLRP3, TLR-4 e citocinas pró-inflamatórias. O treinamento aeróbio de baixa a moderada intensidade reduziu a expressão gênica desses parâmetros e proteica de citocinas pró-inflamatórias, bem como a disfunção autonômica, além de determinar a instalação da bradicardia de repouso. Nossos dados sugerem que a elevada expressão de citocinas pró-inflamatórias no PVN de SHR seja devido à ativação do inflamassoma NLRP3, numa via dependente de TLR-4. Nosso trabalho é o primeiro a investigar o papel de inflamassomas em regiões autonômicas em hipertensos, bem como o efeito do treinamento físico sobre este perfil inflamatório. / The inflammatory process can be triggered by the presence of pathogens (PAMPs) or damaged-associated molecules pattern (DAMPs), this danger signals are recognized by immune system via pattern recognition receptors (PRR) in membrane or in the cytoplasm cells. The activation of NOD like receptors in the cytoplasm can trigger the formation of protein complex called inflammasomes, such as the NLRP3 inflammasome, which is comprised of three basics structures: NOD like receptor, adaptor protein and pro-caspase-1. This complex can induce the proteolytic maturation of pro-inflammatory cytokines (PICs), like interleukin 1 beta (IL-1b) and IL18, which are then released into the extracellular medium. It is known that hypertension is an inflammatory disease associated with DAMPs in blood pressure controlling areas in hypothalamus, like paraventricular nucleus (PVN) and that aerobic training can reverse the deleterious effects of hypertension. So, is our hypothesis that NLRP3 inflammasomes can be active in hypertension and that the exercise training restored the cardiovascular deficits by modulate the innate response. In adult male rats Wistar Kyoto and spontaneously hypertensive rats (SHR), cardiovascular parameters, gene expression of inflammasomes members or cytokines and cytokines protein contents were measured in the PVN of sedentary or four weeks trained groups from both lineages. Our results show that hypertensive animals are characterized by enhanced blood pressure and resting heart rate values, associated with autonomic dysfunction to heart e vessels. SHR had PVN inflammation, what is evidenced by the enhanced inflammasome NLRP3, TLR-4 and PICs expression in this area. The aerobic training with low or moderate intensity reduce the gene expression of these parameters and the protein expression of PICs, as well as, the autonomic dysfunction, in addition to determining the installation of resting bradycardia. Our data suggest that the elevated expression of PICs in SHR PVN is due to the activation of NLRP3 inflammasomes, in a TLR-4 dependent pathway. Our work is the first to investigate the role of inflammasomes in autonomic brain areas in hypertensive rats, as well as, the effect of exercise training on this inflammatory profile.

The risk of injury, inflammation, and oxidative stress increases in skeletal muscle with aging. It has been postulated that pro-oxidant signaling, including upregulation of inducible nitric oxide synthase (iNOS) contributes to inflammation, pathology, and aging in the brain, liver and heart. Exercise training reduces the risk of injury and inflammation. The purpose of this study was: 1) to identify the mechanisms that upregulate iNOS, pro-oxidant and pro-inflammatory signaling in skeletal muscle, and 2) to identify the mechanisms by which exercise training reduces pro-oxidant signaling. Protein levels and activity of iNOS were measured in 4 groups of male Fischer-344 rats (5 mo and 24 mo, n=10/group), old-control (OC), old-trained (OT), young-control (YC), and young-trained (YT). Exercise training protocol was 60 min at 15 m/min at 15° incline for 5 d/wk for 12 wk. Both iNOS protein expression and activity were significantly higher in OC compared to YC, but exercise training reversed the elevation of iNOS levels lower than OC in tibialis anterior. Surprisingly, NF-κB DNA binding activity was significantly lower in OC than YC, while increased with exercise training in white and red gastrocnemius in both OT and YT. In contrast, protein expression of p65, a regulatory subunit of NF-κB was significantly greater in OC than YC, while exercise training significantly reduced p65 in OT compared to OC from the white gastrocnemius. These data indicate that regulation of NF-κB activity with aging is post-translational and alterations in iNOS expression may result from alternative NF-κB pathways. As decreased NF-κB activity with aging could result in downstream increase in pro-apoptotic signaling, we tested follow-up hypotheses that aging would increase pro-apoptotic regulator Bax and decrease the anti-apoptotic regulator Bcl-2. Bax increased while Bcl-2 decreased in OC in white gastrocnemius when compared to YC. In contrast, exercise training resulted in a dramatic upregulation of Bcl-2 and downregulation of Bax protein expression in OT when compared to OC. These novel results indicate that alterations in pro-inflammatory and pro-apoptotic signaling occur in skeletal muscle during the aging process. Importantly, our findings strongly support the hypothesis that exercise training reverses age-induced changes in pro-inflammatory and pro-apoptotic signaling.

The physiological responses to exercise depend on intensity, duration, and type of exercise. The muscles in the body have complex regulation responses in order to create a certain resistance and adaptation to the exercise demands without fatigue. In the following study, we used the model of Alaskan sled dogs in order to analyze changes in gene expression within muscle tissue. Gene expression allows us to look more in depth into temporal or long term biological changes that take place in order for the muscle to adapt and maintain homeostasis. Eight dogs were used for the study; four biopsies from the femoris biceps were taken from each at different time points. Time point 1 (Tp1) untrained dogs, time point 2 (Tp2) after mid training, time point 3 (Tp3) fully trained and time point 4 (Tp4) were taken after dogs had completed a 400 mile run in 4 consecutive days. Time point one was used as a control ratio for the other three time points for analysis one, for the second analysis Tp1 was eliminated as a control. Analysis, one compared Tp2-Tp3 and Tp3-Tp4; the subsequent analysis looked at Tp1-Tp3. For Mid trained animals compared to fully trained, we looked at a total of 25 differentially expressed genes, for fully trained compared against acute exercise performance, we looked at total of 52 differentially expressed genes (based on a ≤0.01 p-value and fold change of ≥3), and untrained was compared to fully trained where we looked at a total of 26 differentially expressed genes. Known transcriptional regulators were mapped from these differentially expressed genes, such as exocyst complex, lysyl oxidase, protein tyrosine phosphatase, protein kinase C, creatine kinase, HSP40, cytochrome P450, ACSL6 gene responsible for Acyl-CoA synthesis, myosin chain, ATP binding, and ubiquitin, among others. These transcripts were linked to important biological pathways, and functional analysis of these pathways demonstrated that changes found in gene expression are responsible for muscle tissue remodeling, energy storage and metabolism changes, cardiovascular enhancement, and activation of elements that regulate metabolism via the nervous system. The following study of transcriptional regulation mechanisms helped identify specific responses to exercise stimuli in the organism that allow the athletes to adapt to the demands of exercise.

The risk of injury, inflammation, and oxidative stress increases in skeletal muscle with aging. It has been postulated that pro-oxidant signaling, including upregulation of inducible nitric oxide synthase (iNOS) contributes to inflammation, pathology, and aging in the brain, liver and heart. Exercise training reduces the risk of injury and inflammation. The purpose of this study was: 1) to identify the mechanisms that upregulate iNOS, pro-oxidant and pro-inflammatory signaling in skeletal muscle, and 2) to identify the mechanisms by which exercise training reduces pro-oxidant signaling. Protein levels and activity of iNOS were measured in 4 groups of male Fischer-344 rats (5 mo and 24 mo, n=10/group), old-control (OC), old-trained (OT), young-control (YC), and young-trained (YT). Exercise training protocol was 60 min at 15 m/min at 15° incline for 5 d/wk for 12 wk. Both iNOS protein expression and activity were significantly higher in OC compared to YC, but exercise training reversed the elevation of iNOS levels lower than OC in tibialis anterior. Surprisingly, NF-&#954;B DNA binding activity was significantly lower in OC than YC, while increased with exercise training in white and red gastrocnemius in both OT and YT. In contrast, protein expression of p65, a regulatory subunit of NF-&#954;B was significantly greater in OC than YC, while exercise training significantly reduced p65 in OT compared to OC from the white gastrocnemius. These data indicate that regulation of NF-&#954;B activity with aging is post-translational and alterations in iNOS expression may result from alternative NF-&#954;B pathways. As decreased NF-&#954;B activity with aging could result in downstream increase in pro-apoptotic signaling, we tested follow-up hypotheses that aging would increase pro-apoptotic regulator Bax and decrease the anti-apoptotic regulator Bcl-2. Bax increased while Bcl-2 decreased in OC in white gastrocnemius when compared to YC. In contrast, exercise training resulted in a dramatic upregulation of Bcl-2 and downregulation of Bax protein expression in OT when compared to OC. These novel results indicate that alterations in pro-inflammatory and pro-apoptotic signaling occur in skeletal muscle during the aging process. Importantly, our findings strongly support the hypothesis that exercise training reverses age-induced changes in pro-inflammatory and pro-apoptotic signaling.

Goldfish subjected to an intermittent short-term aerobic exercise training regime prior to acute hypoxic exposure demonstrated a shift in hypoxia response. Intermittent aerobic training enhanced the aerobic potential of goldfish in the red muscle by increasing maximal activity of citrate synthase by 72% and reduced pyruvate kinase activity by 21% in white muscle. Across red and white muscle tissue, aerobic training caused a decrease in glycogen storage by 19% and 32%, respectively. Liver glycogen stores remained unchanged by training during normoxia. Subsequent hypoxic exposure demonstrated a significant training effect with a77% glycogen depletion in the liver of trained fish compared to a 53% depletion in untrained fish. Hypoxia caused glycogen depletion, glucose mobilization, and ATP depletion in trained and untrained fish muscle tissue. Meanwhile, the liver of trained recovered ATP slower than untrained fish and both liver and plasma had greater lactate accumulation by 1 h hypoxic recovery in trained fish. Alcohol dehydrogenase maximal activity of trained fish responded to hypoxia with a 50% reduction and trained white muscle significantly reduced alcohol dehydrogenase activity during hypoxic recovery. Ethanol was produced with and without training preconditioning in response to hypoxia in red muscle; however, trained fish white muscle showed an ethanol accumulation trend following training and 12 h hypoxia that was significantly cleared during recovery. Ethanol accumulation in white muscle of trained fish may reveal greater perturbation caused by training and hypoxia and/or some developed mechanism for ethanol retention. In effect, this training regime created a very different metabolic profile in goldfish such that during environmental oxygen limitation, trained fish may experience an enhanced metabolic perturbation and greater glycogen depletion which may compromise hypoxic tolerance. / Thesis (Master, Biology) -- Queen's University, 2011-09-30 13:25:36.148

Background: Colorectal cancer (CRC) is the second leading cause of Canadian cancer mortality. Inflammation is a fundamental risk factor in the aetiology of sporadic intestinal carcinoma. Reducing the frequency or duration of gastrointestinal inflammation may decrease CRC risk. Over 200 population studies demonstrate reduced odds of developing CRC among physically active persons. Preliminary data suggests that regular exercise may slow CRC pathogenesis by decreasing and increasing intestinal expression of pro- and anti-inflammatory cytokines, respectively. This research was designed to further our understanding of how exercise influences the colonic cytokine milieu, even in the presence of immunoscenescent changes. Objectives: The objective of the first experiment (Study #1) was to compare cytokine and apoptotic protein expression in intestinal lymphocytes (IL) at baseline and in response to acute exercise-induced oxidant stress in both young and older C57BL/6 female mice. A second objective (Study #2) was to examine the effect of exercise training on the expression of pro- and anti-inflammatory cytokines and pro- and anti-apoptotic proteins in IL of older C57BL/6 female mice under ???resting??? conditions. The final objective (Study #3) was to compare the effect of acute exercise-induced stress on IL cytokine and apoptotic protein expression in trained versus untrained older C57BL/6 mice. Methods: Immediately following sacrifice, plasma was collected from the mice and stored (-80??C) until corticosterone and 8-iso-PGF2?? assessment by enzyme immunoassay. Soleus and plantaris skeletal muscles were excised and frozen in liquid nitrogen (-80??C) until spectrophotometric assessment of cytochrome c oxidase (CO) activity. Finally, the entire mouse intestinal compartment was removed and IL lysates were prepared for flow cytometric analysis of percent apoptosis (% Annexin V+ IL) and for western blot analysis of pro-inflammatory (TNF-??, IL-1??), pleiotropic (IL-6) and anti-inflammatory (IL-10) cytokine, and pro-(caspase-3, -7) and anti-(Bcl-2) apoptotic protein expression. Results: Findings from Study #1 indicate that, in mice, acute exercise increases caspase-3 (IMM and 2Hr groups vs. SED; p<0.05) and TNF-?? (IMM vs. SED and 2Hr groups; p<0.001), and decreases Bcl-2 (IMM and 2Hr groups vs. SED; p<0.01) expression in intestinal lymphocytes. Furthermore, IL expression of Bcl-2 was lower (p<0.001) and % Annexin V+ IL was higher (p<0.05) in the older vs. young mice. The results from Study #2 indicate that trained older mice had lower (p<0.05) expression of TNF-?? and caspase-7 in IL, and lower (p<0.05) concentration of 8-iso-PGF2?? in plasma compared to sedentary untrained controls. Finally, Study #3 shows that older trained mice display increased expression of pro-(TNF-??) and anti-(IL-10) inflammatory cytokines and pro-apoptotic (caspase-3, caspase-7) proteins, and decreased expression of anti-apoptotic (Bcl-2) protein in IL after acute exercise challenge compared to older untrained controls. In both Study #1 & #3, the treadmill protocol induced stress: plasma corticosterone and 8-iso-PGF2?? were higher in mice sampled immediately after acute exercise relative to the no acute exercise (sedentary) condition. This exercise effect did not differ by age (Study #1) or by training (Study #3) condition. In addition, Study #2 & Study #3 showed elevations in cytochrome c oxidase activity following long-term training. Conclusion: Collectively, these results suggest that, in C57BL/6 female mice, IL expression of pro-apoptotic proteins and pro-inflammatory cytokines does not differ by age (young vs. older animals) in response to a single intense exercise bout. However, older mice display lower expression of ???protective??? anti-apoptotic proteins and a higher percentage of early apoptotic IL compared to young mice. Additionally, long-term exercise may protect the bowel from inflammation by reducing inflammatory cytokine and apoptotic protein expression under ???resting??? (no stress) conditions. Finally, long-term training preserves the IL cytokine and apoptotic protein responses in older mice to a magnitude similar to that previously described in young mice. Alternatively, older untrained mice display reduced responsiveness to acute treadmill exercise, suggestive of immunosenescence.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O exercício contínuo de baixa intensidade é capaz de atenuar a hipertrofia da célula muscular lisa da parede da aorta de ratos espontaneamente hipertensos (SHR), e parece atuar sobre a distribuição de fibras oxitalânicas, elaunínicas e elásticas. As alterações funcionais das grandes artérias relacionadas com a idade, deposição de colágeno e elastina na parede arterial e a elasticidade, são também melhoradas com a atividade física. No presente trabalho objetivamos estudar os efeitos da atividade física aeróbica de baixa intensidade no remodelamento estrutural da artéria aorta em modelo de hipertensão genética de ratos SHR. Através da análise da distribuição das fibras oxitalânicas, elaunínicas e elásticas na aorta dos animais controles e SHR submetidos ou não a atividade física de baixa intensidade. Foram utilizados 32 ratos, sendo 16 ratos SHR machos e 16 ratos normotensos Wistar Kyoto (WKY) machos com 8 semanas de idade. Ratos machos foram alocados em 4 grupos: WKY sedentário (WKY-SED), WKY exercitado (EX-WKY), SHR sedentário (SED-SHR), e SHR exercitado (EX-SHR). Os ratos sedentários foram limitados à atividade na caixa, enquanto que os ratos exercitados foram submetidos a um exercício de 1 h / dia, 5 dias / semana. Esses grupos passaram pelo protocolo de atividade física de 20 semanas e a pressão arterial foi mensurada semanalmente (PA). As aortas foram colhidas e processadas para microscopia de luz, microscopia eletrônica e western blotting. Foram realizadas as colorações orcinol neo-fucsina e resorcina-fucsina de Weigert. No grupo hipertenso, o exercício mantém a PA em um nível relativamente semelhante ao inicio do protocolo, mostrando a capacidade de prevenir o aumento da PA ao longo das 20 semanas. No grupo dos animais hipertensos não tratados, a PA aumenta. A PA aumentou progressivamente nos ratos SED-SHRs atingindo 1894 mmHg, mas o exercício físico impediu este processo. Ao final do experimento a PA nos ratos EX-SHRs foi similar o dos ratos WKY (1184 vs. 1144 mmHg), respectivamente. Observou-se maior expressão de elastina e maior distribuição de fibras oxitalânicas, elaunínicas e elásticas em animais que foram submetidos ao protocolo de exercício físico. A porcentagem de fibras elásticas e oxitalânicas foi menor em SED-SHR comparado com SED-WKY, mas o exercício físico aumentou a porcentagem dessas fibras em ambos os grupos. Através da imuno-histoquímica ultra-estrutural para elastina e fibrilina, os grupos EX-WKY e EX-SHR apresentaram uma marcação mais intensa para elastina e fibrilina. Animais hipertensos que não sofreram o protocolo de exercício físico apresentam espessura da parede da aorta maior que a dos animais que sofreram o exercício. O número de lamelas elásticas, bem como as fibras oxitalânicas e elaunínicas, é maior no grupo EX-SHR, em relação ao SED-SHR. Os grupos exercitados tiveram maior expressão de eNOS que seus respectivos grupos sedentários, e as células endoteliais apresentaram características morfológicas preservadas. A associação da atividade física com modelos de hipertensão genética mostra que o exercício físico tem efeitos benéficos nessa situação, uma vez que atenua a hipertensão e o remodelamento adverso da parede da aorta. / The continuous exercise of low intensity is able to attenuate the hypertrophy of smooth muscle cells in the wall of the aorta of spontaneously hypertensive rats (SHR), and it seems work on the distribution of fiber oxytalan, elaunínicas and elastic. The functional changes of large arteries associated with age, deposition of collagen and elastin in the arterial wall and elasticity are also improved with physical activity. In the present study investigated the effects of aerobic physical activity of low intensity in the structural remodeling of the aorta in genetic model of hypertension in SHR rats. By analyzing the distribution of fiber oxytalan, elaunínicas and elastic in the aorta of SHR and control animals submitted or not the physical activity of low intensity. We used 32 rats, and 16 rats SHR male rats and 16 normotensive Wistar Kyoto (WKY) males with 8 weeks of age.Male rats were divided into 4 groups: sedentary WKY (WKY-SED), exercised WKY (WKY-EX), sedentary SHR (SHR-SED) and exercised SHR (SHR-EX). The rats were limited to sedentary activity box, while the rats were trained on an exercise to 1 h / day, 5 days / week. They passed by the Protocol of 20 weeks of physical activity and blood pressure was measured weekly (BP). Aortas were harvested and processed for light microscopy, electron microscopy and western blotting. Orcinol neo-fuchsin staining were performed and resorcin-fuchsin of Weigert. In the hypertensive group, the exercise keeps the blood pressure in a relatively similar to the start of the protocol, showing the ability to prevent the increase in PA over the 20 weeks. In the group of untreated hypertensive animals, the PA increases. BP increased progressively in rats SED-SHRs reached 189 4 mmHg, but the exercise prevented this process. At the end of the experiment the PA in rats EX-SHRs was similar to the WKY rats (118 4 vs. 114 4 mmHg), respectively. There was increased expression of elastin and increased distribution of fiber oxytalan, elaunínicas and elastic in animals that were subjected to the protocol of exercise. The percentage of elastic fibers and oxytalan was lower in SHR-SED compared with WKY-SED, but exercise increased the percentage of fibers in both groups. By immuno-histochemical ultrastructural for elastin and fibrillin, both groups EX-EX-SHR and WKY showed a stronger mark for elastin and fibrillin. Hypertensive animals that have not been the protocol of exercise have wall thickness of the aorta higher than that of animals that underwent the exercise. The number of elastic lamellae, and the fibers and oxytalan elaunínicas, is greater in the EX-SHR group, for the SHR-SED. The exercise groups had a higher expression of eNOS to their respective sedentary groups, and the endothelial cells showed morphological features preserved. The association of physical activity with genetic models of hypertension shows that exercise has beneficial effects in this situation, since hypertension and reduces the adverse remodeling of the aortic wall.

Ageing is associated with declines in cardiorespiratory and muscular fitness; yet for older adults the ability to perform the basic tasks of daily living is partly dependent on upperand lower-body fitness. Exercise training is an effective approach to counteract these age associated declines, with combined exercise training and high-intensity interval training (HIT) capable of eliciting improvements in cardiorespiratory and muscular fitness simultaneously. Recently, a new hydraulic resistance exercise machine (Speedflex) has been developed with potential to be a viable training mode for older adults allowing users to perform high speed movements with upper- and lower-body muscles. Accordingly, the aim of this thesis was to evaluate the potential effectiveness of Speedflex as a training strategy in older adults. Initially, this work sought to determine the feasibility of performing exercise training using Speedflex in older adults by quantifying the acute training responses to 1) HIT and 2) strength training and comparing these against criterion exercise modes. Here, the observed physiological and perceptual responses demonstrated that Speedflex is a feasible mode of exercise training in older adults, capable of inducing a high-intensity training stimulus. Following this, a systematic review and meta-analysis was performed to quantify the effects of same-session combined exercise training in older adults with results demonstrating possibly small to possibly large beneficial effects on measures of fitness. As muscle power appears to be a critical determinant of physical functioning in older adults, chapter five evaluated the reliability of the Nottingham leg extensor power rig, finding it to be reliable both short- and long-term, thereby confirming its suitability as a primary outcome measure for the final study and providing data for sample size estimation. Finally, chapter six evaluated the effects of a 12-week combined upper- and lower-body HIT intervention using Speedflex on physical fitness in older adults. Clear beneficial improvements were observed for participants in the intervention group compared to those in the control group for maximal oxygen uptake (~8%), muscle power (~10%) and muscle strength (~6%). The findings presented in this thesis demonstrate that both same-session combined training and HIT performed using Speedflex are capable of simultaneously improving cardiorespiratory and muscular fitness in older adults.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O exercício contínuo de baixa intensidade é capaz de atenuar a hipertrofia da célula muscular lisa da parede da aorta de ratos espontaneamente hipertensos (SHR), e parece atuar sobre a distribuição de fibras oxitalânicas, elaunínicas e elásticas. As alterações funcionais das grandes artérias relacionadas com a idade, deposição de colágeno e elastina na parede arterial e a elasticidade, são também melhoradas com a atividade física. No presente trabalho objetivamos estudar os efeitos da atividade física aeróbica de baixa intensidade no remodelamento estrutural da artéria aorta em modelo de hipertensão genética de ratos SHR. Através da análise da distribuição das fibras oxitalânicas, elaunínicas e elásticas na aorta dos animais controles e SHR submetidos ou não a atividade física de baixa intensidade. Foram utilizados 32 ratos, sendo 16 ratos SHR machos e 16 ratos normotensos Wistar Kyoto (WKY) machos com 8 semanas de idade. Ratos machos foram alocados em 4 grupos: WKY sedentário (WKY-SED), WKY exercitado (EX-WKY), SHR sedentário (SED-SHR), e SHR exercitado (EX-SHR). Os ratos sedentários foram limitados à atividade na caixa, enquanto que os ratos exercitados foram submetidos a um exercício de 1 h / dia, 5 dias / semana. Esses grupos passaram pelo protocolo de atividade física de 20 semanas e a pressão arterial foi mensurada semanalmente (PA). As aortas foram colhidas e processadas para microscopia de luz, microscopia eletrônica e western blotting. Foram realizadas as colorações orcinol neo-fucsina e resorcina-fucsina de Weigert. No grupo hipertenso, o exercício mantém a PA em um nível relativamente semelhante ao inicio do protocolo, mostrando a capacidade de prevenir o aumento da PA ao longo das 20 semanas. No grupo dos animais hipertensos não tratados, a PA aumenta. A PA aumentou progressivamente nos ratos SED-SHRs atingindo 1894 mmHg, mas o exercício físico impediu este processo. Ao final do experimento a PA nos ratos EX-SHRs foi similar o dos ratos WKY (1184 vs. 1144 mmHg), respectivamente. Observou-se maior expressão de elastina e maior distribuição de fibras oxitalânicas, elaunínicas e elásticas em animais que foram submetidos ao protocolo de exercício físico. A porcentagem de fibras elásticas e oxitalânicas foi menor em SED-SHR comparado com SED-WKY, mas o exercício físico aumentou a porcentagem dessas fibras em ambos os grupos. Através da imuno-histoquímica ultra-estrutural para elastina e fibrilina, os grupos EX-WKY e EX-SHR apresentaram uma marcação mais intensa para elastina e fibrilina. Animais hipertensos que não sofreram o protocolo de exercício físico apresentam espessura da parede da aorta maior que a dos animais que sofreram o exercício. O número de lamelas elásticas, bem como as fibras oxitalânicas e elaunínicas, é maior no grupo EX-SHR, em relação ao SED-SHR. Os grupos exercitados tiveram maior expressão de eNOS que seus respectivos grupos sedentários, e as células endoteliais apresentaram características morfológicas preservadas. A associação da atividade física com modelos de hipertensão genética mostra que o exercício físico tem efeitos benéficos nessa situação, uma vez que atenua a hipertensão e o remodelamento adverso da parede da aorta. / The continuous exercise of low intensity is able to attenuate the hypertrophy of smooth muscle cells in the wall of the aorta of spontaneously hypertensive rats (SHR), and it seems work on the distribution of fiber oxytalan, elaunínicas and elastic. The functional changes of large arteries associated with age, deposition of collagen and elastin in the arterial wall and elasticity are also improved with physical activity. In the present study investigated the effects of aerobic physical activity of low intensity in the structural remodeling of the aorta in genetic model of hypertension in SHR rats. By analyzing the distribution of fiber oxytalan, elaunínicas and elastic in the aorta of SHR and control animals submitted or not the physical activity of low intensity. We used 32 rats, and 16 rats SHR male rats and 16 normotensive Wistar Kyoto (WKY) males with 8 weeks of age.Male rats were divided into 4 groups: sedentary WKY (WKY-SED), exercised WKY (WKY-EX), sedentary SHR (SHR-SED) and exercised SHR (SHR-EX). The rats were limited to sedentary activity box, while the rats were trained on an exercise to 1 h / day, 5 days / week. They passed by the Protocol of 20 weeks of physical activity and blood pressure was measured weekly (BP). Aortas were harvested and processed for light microscopy, electron microscopy and western blotting. Orcinol neo-fuchsin staining were performed and resorcin-fuchsin of Weigert. In the hypertensive group, the exercise keeps the blood pressure in a relatively similar to the start of the protocol, showing the ability to prevent the increase in PA over the 20 weeks. In the group of untreated hypertensive animals, the PA increases. BP increased progressively in rats SED-SHRs reached 189 4 mmHg, but the exercise prevented this process. At the end of the experiment the PA in rats EX-SHRs was similar to the WKY rats (118 4 vs. 114 4 mmHg), respectively. There was increased expression of elastin and increased distribution of fiber oxytalan, elaunínicas and elastic in animals that were subjected to the protocol of exercise. The percentage of elastic fibers and oxytalan was lower in SHR-SED compared with WKY-SED, but exercise increased the percentage of fibers in both groups. By immuno-histochemical ultrastructural for elastin and fibrillin, both groups EX-EX-SHR and WKY showed a stronger mark for elastin and fibrillin. Hypertensive animals that have not been the protocol of exercise have wall thickness of the aorta higher than that of animals that underwent the exercise. The number of elastic lamellae, and the fibers and oxytalan elaunínicas, is greater in the EX-SHR group, for the SHR-SED. The exercise groups had a higher expression of eNOS to their respective sedentary groups, and the endothelial cells showed morphological features preserved. The association of physical activity with genetic models of hypertension shows that exercise has beneficial effects in this situation, since hypertension and reduces the adverse remodeling of the aortic wall.