Previous work has demonstrated that endothelial dysfunction (ED) plays a pivotal role in the development and progression of atherosclerosis. Several risk factor that increase the risk of ED have been identified; including hypoxia and ageing; however, most of the research only asses the degree of impairment in a single vascular bed (micro or large blood vessels). Similarly, studies investigating the potential influence of various therapies for ED, fail to account for the heterogeneity of the endothelium. The overall objective of the present thesis was to measure systemic endothelial responses (microvascular and large vascular beds) to acute hypoxia, and to assess the potential benefit of dietary nitrate (NO3-) therapy on systemic endothelial function (EF). The specific aims of the first study (Chapter 2) were to determine the effects of acute hypoxia on microvascular and large-vessel EF [via non-invasive laser Doppler imaging (LDI) with acetylcholine (ACh) iontophoresis, and flow-mediated dilatation (FMD)], respectively]. Compared to normoxia, endothelium-dependent microvascular dilation was reduced after 30 minutes of exposure (x̃Δ = -109%, {IQR: 542.7}, p = 0.05). Alternatively, hypoxia did not affect endothelium-independent microvascular function after 30 minutes of exposure. Compared to normoxia, hypoxia significantly reduced allometrically scaled FMD responses after 60 min (x̅Δ-1.21%, p < 0.001). The magnitude of the decline in microvascular EF was correlated with cardiorespiratory fitness (r = 0.45, p = 0.02), but was not associated with large-vessel EF (r = -0.09 = p = 0.68). This study concluded that acute exposure to hypoxia reduced endothelium-dependent vascular function, in micro and large vascular beds. The decline in microvascular EF was approximately twice as large as that observed in the large blood vessel, demonstrating the heterogenous responses of the endothelium. Study 2 (Chapter 3) examined the effects of a 4-week dietary NO3- intervention (beetroot juice (BRJ)) vs. placebo (PLA) on microvascular and large-vessel EF [via non-invasive LDI with ACh iontophoresis, and FMD] in healthy older adults. Plasma NO3- increased following 2-weeks of dietary NO3- supplementation (p < 0.05) along with a concomitant improvement in systolic and diastolic blood BP (−6mmHg and −4mmHg, respectively) (p < 0.05). However, there were no significant differences in endothelium-dependent or endothelium-independent microvascular function between groups. FMD increased by 1.5% following 2-weeks of dietary NO3- and were sustained until week 4 (p < 0.05), with only a minimal (0.1%) change for the PLA group. This study concluded that chronic dietary NO3- ingestion significantly improves BP and large-vessel EF in healthy older adults. However, 4-weeks of BRJ did not alter microvascular function. To conclude, the present work highlights the importance of assessing EF in multiple vascular beds when investigating endothelial response to harmful stimuli or therapeutics. Acute hypoxia significantly reduces microvascular and large-vessel EF in healthy young adults. The decrease in microvascular EF was two-fold greater than the observed reduction in large-vessel EF. Secondly, the present work demonstrated that dietary NO3- supplementation significantly improved large-vessel EF in healthy older adults. However, no microvascular EF improvements were detected. Collectively, these findings emphasise the importance of assessing EF in multiple vascular beds.