Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo - Relevance to endothelial dysfunction in hypercholesterolemia

Flow-mediated dilatation (FMD) of conduit arteries is dependent on an intac t endothelium, although the mechanisms are not fully understood. Using high -resolution ultrasound, we examined the role of endothelial mediators in ra dial artery dilatation in response to transient (short period of reactive h yperemia) and sustained (prolonged period of reactive hyperemia, hand warmi ng, or an incremental infusion of acetylcholine into the distal radial arte ry) hyperemia. After short episodes of reactive hyperemia, FMD was abolishe d by local infusion of the nitric oxide synthesis inhibitor N(G)monomethyl- L-arginine (5.3+/-1.2% versus 0.7+/-0.7%, P<0.001). In contrast, basal vess el diameter and dilatation after prolonged episodes of reactive hyperemia, hand warming, and distal infusion of acetylcholine were not attenuated by n itric oxide synthesis inhibition. Inhibition of cyclooxygenase or local aut onomic nervous system blockade also had no effect on FMD. Patients with hyp ercholesterolemia exhibited reduced FMD in response to transient hyperemia, but the response to sustained hyperemia was normal. These data suggest het erogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus. Dilatation after brief episodes of h yperemia is mediated by release of nitric oxide, whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition. Hypercholeste rolemia seems to differentially affect these pathways with impairment of th e nitric oxide-dependent pathway and preservation of non nitric oxide-media ted dilatation to sustained flow stimuli.