| Popis: |
Pressure and wire myography are established techniques for the study of small artery structure and function. The series of studies in this thesis have evaluated these techniques in a variety of novel clinical settings in which microvascular dysfunction has not been evaluated previously. In health, normal small artery function is likely to serve a number of different important functions. Changes to basal tone will affect peripheral resistance and thus blood pressure. Furthermore, by regulation of downstream nutritive flow the arterial tone will also influence glycaemia. The myogenic capacity ofthe artery, by constricting and remodeling against higher intraluminal pressure, serves to protect vulnerable downstream capillary beds from elevated central pressures in hypertension. We have shown for the first time that healthy perivascular adipose tissue exerts an anticontractile effect on the adjacent small artery by release of adiponectin. In patients with obesity and metabolic syndrome, this capacity is lost due to inflammation in the adipose tissue. However, we have shown that improvements to metabolic control in patients with Type 1 Diabetes over a 10 year period can reverse the characteristic abnormal hypertrophic remodeling caused by hypertension in diabetes and instead enable eutrophic remodeling which is more commonly seen in patients without diabetes. In the final clinical study, we show that patients with late-life depression, a model of cerebral microvascular target organ damage, despite being matched with control participants for traditional risk factors (diabetes, blood pressure, cholesterol), show impaired small artery endothelial function and abnormal hypertrophic growth of the vessel wall. Lastly, in an animal model with controlled genetic mutations in the cytoskeleton protein adducin, we have shown that deficiencies in the beta subunit affect renal artery myogenic tone which is associated with the development of proteinuria. |
