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Obesity related hypertension represents a significant clinical problem with an increasing prevalence. Hypertension is a primary risk factor of retinal and kidney damage, heart disease and stroke. Thus, elucidating the specific mechanisms underlying obesity-related hypertension may translate into much needed novel therapies to tackle this disease. In this thesis, a mouse model of diet-induced obesity (DIO) exhibiting hypertension and abnormalities in glucose handling were studied in an attempt to identify pathological mechanisms driving obesity-related hypertension. Isolated third-order mesenteric arteries from high-fat fed diet-induced obese mice and low-fat fed lean control mice were studied to examine endothelial and vascular smooth muscle vasodilatory function. Treatment of pressurised isolated arteries with carbachol (1-10 μM) did not find any reduction in endothelium-dependent dilatation as a result of DIO. Endothelial TRPV4 ion channels and endothelial K+ channels, which have been shown to be critical in mediating endothelium-dependent hyperpolarisation-mediated vasodilation after treatment with acetylcholine/carbachol, were also found to be unaffected by DIO. Consistent with this, high-speed confocal imaging of endothelial cells in arterial preparations from DIO mice loaded with fluo-4 AM, a Ca2+ probe, did not find any significant differences in the characteristics of TRPV4 channel-mediated Ca2+ signalling compared to age-matched lean control mice. Experiments on pressurised arteries revealed that arteries from DIO mice exhibited increased myogenic tone and reduced activation of large-conductance Ca2+ activated K+ (BK) channels within vascular smooth muscle cells. Treatment with a pharmacological agonist of BK channels found equivalent functional vasodilatory capacity between DIO and control mice. This led to investigations of upstream Ca2+ sparks, representing release of stored Ca2+ from the sarcoplasmic reticulum through ryanodine receptors capable of activating nearby BK channels, in fluo-4 AM-loaded pressurised arteries. Arteries from lean control mice displayed an increase in Ca2+ spark frequency in response to physiological intraluminal pressures as published recently1; the novel finding here supports that this intraluminal pressure-dependent effect was lost in arteries from DIO mice which may explain the increased myogenic tone, reduced BK channel activity and mild hypertension in these mice. Intraluminal pressure-induced increase of Ca2+ sparks is proposed to rely on oxidant-activation of cyclic guanosine monophosphate-activated protein kinase-1α. For this to occur, it is hypothesised that intraluminal pressure leads to the production of ROS; therefore, 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate-loaded wild-type arteries were studied to test this hypothesis. It was found that normal physiological pressures within small arteries (80 mmHg) led to increased levels of ROS compared to arteries left at low intraluminal pressure (20 mmHg). This suggests that vascular smooth muscle cells are able to sense intraluminal pressure, produce ROS as a result and oxidise cyclic guanosine monophosphate-activated protein kinase-1α to regulate Ca2+ sparks and BK channel-mediated myogenic relaxation and direct blood flow appropriately. The exact identities of these ROS are not currently known and further experimentation should look to answer this question alongside investigating the cellular source of these ROS. Overall, it appears that endothelial vasodilatory function of small resistance arteries remains intact in DIO in mice, but there is an increase in myogenic tone. This appears to be a result of reduced BK channel-mediated hyperpolarisation and vasodilation due to a failure of intraluminal pressure-induced increases in Ca2+ spark frequency within vascular smooth muscle cells. Further work is necessary to identify if there is a dysfunction in intraluminal pressure induced production of ROS in DIO.