Abstract

Peripheral vascular disease is associated with altered blood flow dynamics and microvascular function. The vascular endothelium is a significant contributor to cardiovascular health and microvascular tone via the release of known endothelium-derived relaxing factors. The aim of this study was to examine endothelium-dependent and endothelium-independent function in small resistance arteries in an attempt to identify potential mechanism underlying lower limb ischaemia. Resistance arteries were isolated from 26 male subjects with ischaemic peripheral vascular disease. Skeletal muscle biopsies were taken from proximal skeletal muscle (PSM) non-ischaemic and distal skeletal muscle (DSM) ischaemic sites and structure and function compared. Significant endothelium-dependent dysfunction was observed in DSM resistance arteries when compared with PSM. Endothelial dysfunction appears exclusive to loss of endothelium-derived nitric oxide whereas endothelium-derived hyperpolarizing factor type mediated relaxation appears to be up regulated. The loss of endothelium-dependent phosphorylation of eNOS was correlated with increased expression of the negative regulator caveolin-1. Expression of total eNOS and heat shock protein 90 were unaffected. These data provide novel insight into the mechanism underlying significant loss of endothelial vascular homeostatic control mechanisms in human resistance arteries. This study provides further understanding of vascular pathogenesis in peripheral vascular disease highlighting the pathological adaptation and restorative compensatory mechanism of the endothelium in resistance arteries.