The regulation of pulmonary blood flow and ventilation during exercise is mediated by numerous factors, yet the role of certain cardiovascular and pulmonary reflex control systems is unknown. Therefore this thesis investigated the pulmonary vascular response to the activation of the muscle metaboreflex alone, and combined with activation of the muscle mechanoreflex. The ventilatory responses to the activation of the muscle metaboreflex were also studied under a background of activated ventilatory chemoreceptors. Finally the effect of increased metabolism on the ventilatory sensitivity to carbon dioxide was investigated in healthy humans. We found that activation of the muscle metaboreflex induced pulmonary vasoconstriction that was alleviated by muscle mechanoreflex activation. Furthermore a respiratory response to the activation of the muscle metaboreflex was observed in hypercapnia but not when breathing room air. Finally we found that increases in metabolic rate induced elevations in the ventilatory sensitivity to carbon dioxide. Overall these data suggest that the interplay between cardiovascular and respiratory control systems contribute to the regulation of pulmonary haemodynamics and breathing during exercise. Our findings could be implicated in the reduced exercise tolerance seen in chronic heart failure patients.

Individual Zone of Optimal Functioning (IZOF) model has garnered empirical support to explain states of human functioning and its subsequent impact on sport performance. Research suggests athletes’ who are able to regulate performance states, that allow for utilization of resources to complete the task in hand, are more likely to experience superior performance. Yet minimal research has examined how the IZOF model may inform intervention programs to ensure athletes’ skills in regulation are enhanced. The present thesis aimed to explore the usefulness of the IZOF model as a guiding framework in real-world applied settings for enhancing athlete regulation of performance states during competition. In study one a practitioner-focused action research study examined the “how” of working within an IZOF framework. In study two, a multiple case study examined the influence of an IZOF program on athletes’ pre- and post-intervention thoughts, feelings, regulatory actions, and subsequent performance. A qualitative examination of this program from the athletes’ perspective highlighted key program processes and outcomes (study three). An identified outcome of well-being was subsequently examined in relation to athlete use of regulation techniques and skills in study four. This thesis highlights several implications for practitioners when adopting the IZOF model in applied practice.

There is a large inter-subject variability in the capacity to oxidise fat (MFO) during exercise and this could have important implications for metabolic health. Chapter 3 of this thesis was designed to explore the relationship between MFO with 24-h fat oxidation and insulin sensitivity. This study showed that MFO during exercise is significantly and positively associated with 24-h fat oxidation and insulin sensitivity. Chapter 4 investigated relationships between selected plasma metabolites, hormones and overnight-fasted resting fat oxidation rates, with MFO. Plasma lipolytic markers, plasma insulin, resting fat oxidation and aerobic capacity were important modulators of the inter-subject variability in MFO. Chapter 5 explored the influence of meal timing around exercise on substrate utilisation, lipolytic markers and insulin, and intra-muscular triglyceride (IMTG) use in obesity. This study found that Fasted- as compared with Fed-state exercise augments exercise fat oxidation, and the circulating concentration of plasma glycerol and NEFA during exercise. This thesis generates new data that contributes to our understanding of the links between MFO and metabolic risk, as well as the factors that influence the inter-subject variability in MFO during exercise. It also shows that fasted exercise augments exercise fat oxidation, which could have meaningful implications for optimising metabolic health.

Over two thirds of the UK population do not meet physical activity (PA) recommendations set by the Department of Health (2011) to improve or maintain health. It is therefore essential to focus research on effective and efficient methods to promote autonomous reasons to engage and persist in PA. Employing a variety of research designs this thesis explores the social contextual and environmental determinants, predominantly from a Self-Determination Theory perspective, of PA adoption, persistence and psychological well-being (Study 1; qualitatively). Study 2 and 3 examined unique sources of support from within and beyond a PA programme including human and non-human sources (i.e., technology). Study 3 employed an intervention focusing on the effect of autonomy supportive text messages on PA behaviour and well-being. Deriving from findings of Study 1, the final study (4) investigated the effect of the physical environment and PA levels on affective states. Results highlight the importance and relevance of socio-contextual (considering each unique contribution of individual sources of support) and environmental determinants (moderate intensity PA within a natural outdoor environment being key for positive high activation) in the promotion of PA. Findings carry important practical implications for those involved in promotion of long-term PA behaviour.

This thesis investigated the role of O\(_2\)-dependent substances in mediating the vasodilatation seen following exercise (post-exercise hyperaemia) and in fatigue development. Additionally we compared young and old subjects to investigate the effects of ageing in both of these phenomena. Breathing supplementary 40% O\(_2\) during handgrip exercise at 50% of maximum voluntary contraction had no effect of the magnitude of post-exercise hyperaemia compared to air breathing control. Furthermore, aspirin administration did not alter magnitude of post-exercise hyperaemia or the levels of prostaglandin E metabolites assayed from the forearm venous efflux. Similarly the magnitude of post-exercise hyperaemia was not affected by aminophylline administration. Collectively these suggest that prostaglandins and adenosine are not obligatory mediators of post-exercise hyperaemia. Supplementary O\(_2\) breathed during recovery had no effect on fatigue in a second bout of exercise or any of the substances proposed to mediate fatigue, in young subjects. We demonstrated that older subjects showed no changes in the magnitude of post-exercise hyperaemia, but they were more fatigue resistant. There was no O\(_2\)-dependence of either post-exercise hyperaemia or fatigue in older subjects. In conclusion, we have found no evidence of O\(_2\)-dependent mediators in either post-exercise hyperaemia or fatigue.

The principle aims of this thesis involved the development of methods to measure enzymes that determine nitric oxide (NO) production (eNOS) and quenching (NAD(P)Hoxidase) within the microvasculature of skeletal muscle, and the use of these techniques to investigate metabolic syndrome and various training modes. Chapter 2 describes the development of reliable methods to analyse enzymes responsible for NO bioavailability within the endothelium of skeletal muscle microvessels. Chapter 3 suggests that impaired eNOS ser1176 phosphorylation is instrumental to the reductions in insulin sensitivity of obese Zucker rats. Chapter 4 reveals that 6 weeks endurance training (ET) and sprint interval training (SIT) in sedentary males induce similar increases in capillary density, and that SIT is more effective than ET at increasing eNOS content. Chapter 5 fails to observe a change in any measure of microvascular structure or function following 6 weeks resistance training in sedentary males. Chapter 6 suggests that 4 weeks of constant-load SIT is an effective intervention to improve the content of endothelial enzymes controlling NO bioavailability in obesity. In conclusion this thesis describes novel techniques which will be valuable tools for future research into microvascular function, and suggests that SIT may be an effective time efficient strategy to improve microvascular function.

An accumulation of epidemiological studies along with several lines of experimental research highlight sustained elevated resting heart rate as a significant predictor of cardiovascular morbidity and mortality. However, resting heart rate as a simple and inexpensive clinical parameter often remains overlooked by physicians. We therefore sought to raise awareness concerning the detrimental role of elevated resting heart rate in cardiovascular disease. Using three separate large prospective cohort studies, we examined the clinical importance of accelerated resting heart rate as a robust predictor of adverse cardiovascular prognosis. The current data supports the contention that a raised resting heart rate amplifies the risk of having several cardio-metabolic risk factors including type 2 diabetes mellitus, the metabolic syndrome, and increased pulse wave velocity. Resting tachycardia also appeared to increase the risk of cardiovascular mortality in otherwise healthy individuals, as well as negatively predicting outcome in patients already at-risk for the condition. Notably, we observed a strong synergistic effect between inflammatory activity and concurrent elevated resting heart rate among those who experienced a cardiovascular event. Overall, these findings underline the relevance of a high resting heart rate in the pathogenesis of atherosclerosis and in the clinical manifestations of cardiovascular mortality.

This thesis aimed to investigate a novel way to explore changes in gaze behaviour, whilst walking, in frail populations. Initially three studies were conducted to establish how similar gaze behaviour recorded during walking was to that recorded whilst scene viewing. Duration of time and number of times different features were fixated were found to be similar in the three experiments. Older adults were assessed for falling risk and split into higher risk of falling (HROA) and lower risk of falling (LROA) groups. Their gaze behaviour was recorded whilst scene viewing along with a group of young adults. HROA were found to fixate the travel path longer than LROA and younger adults. HROA were slower at completing the incongruent Stroop task, suggesting a relationship between response inhibition and increased falling risk. A group of stroke patients were assessed for falling risk and split according to lesion location (parietal, occipital or frontal-temporal); gaze behaviour was recorded during scene viewing and compared to controls. Observable differences, which related to falling risk and lesion location, were shown in the gaze behaviour of the stroke patients compared to the controls. The findings of this thesis suggest that scene viewing could be used to better inform us about the changes in gaze behaviour which occur in frail populations that led to an increased risk of falling and the cognitive mechanisms which underlie these changes than laboratory studies.

Increase in body temperature is a major factor limiting endurance performance in the heat and it is shown in this thesis that the effects of raised body temperature on performance, perception and neuroendocrine response to exercise are mediated by an interaction of body temperatures. Prolactin has been used as an indicator of hypothalamic activity and the pathways regulating its release have been investigated using pindolol as a 5-HT\(_ \) antagonist. The prolactin response to a buspirone challenge has been shown to be approximately 50% serotonergic and 50% dopaminergic, but with a wide inter-subject variation. Passive heating is a potent stimulus for prolactin release and it was shown that 5-HT\(_ \) stimulation plays virtually no part in this process, raising the possibility that prolactin release during hyperthermic exercise may also be largely due to withdrawal of dopamine inhibition. A comparison of exercise tolerance in the heat and the sensitivity of central serotonergic and dopaminergic pathways further indicates the importance of dopamine in central fatigue. The action of caffeine in enhancing endurance performance has been shown not to involve the hypothalamus and this draws attention to other pathways that may be involved in central fatigue including the basal ganglia and limbic system.

Low levels of cardio-respiratory fitness represent a major health risk. Few studies have investigated the possible contribution of psychological influences to cardio-respiratory fitness, with none longitudinally. The purpose of the present thesis was to explore the cognitive and behavioural correlates of adults’ cardio-respiratory fitness using theoretical constructs forwarded in Self-Determination Theory (SDT; Deci & Ryan, 2000) and the Theory of Planned Behaviour (TPB; Azjen, 1991). Studies 1 and 3 tested potential contributions of the Self Determination Theory cognitions of autonomous (intrinsic and identified) and controlled (introjected and external) motivations, including amotivation, to cardio-respiratory fitness over 9 weeks and 3 years. Studies 2 and 4 tested potential contributions from the Theory of Planned Behaviour constructs of intention, attitude, subjective norm and perceived behavioural control to cardio-respiratory fitness over the same time period. Analysis from structural equation modelling revealed only intrinsic motivation and affective attitude, constructs from the SDT and TPB respectively, contributed to changes in fitness. Collectively, the four studies suggest that intrinsic motivation and affective attitude are of major importance to cardio-respiratory fitness, even when individuals may have prominent controlled reasons for participating in exercise. The findings provide a foundation for theoretically aligned future research investigating the psychosocial antecedents of exercise with a view to developing more effective theory driven lifestyle interventions directed at enhancing this important health outcome.