© 2001 American Heart Association, Inc.
Clinical Research |
Heterogenous Nature of Flow-Mediated Dilatation in Human Conduit Arteries In Vivo
Relevance to Endothelial Dysfunction in Hypercholesterolemia
From the Vascular Physiology Unit, Institute of Child Health (M.J.M., A.E.D., M.T., J.E.D.) and the Centre for Clinical Pharmacology, University College London (R.K.K., J.C., P.V., R.J.M.), London, UK.
Correspondence to Dr M.J. Mullen, Vascular Physiology Unit, Great Ormond Street Hospital for Children, NHS Trust, Great Ormond St, London WC1N 3JH UK. E-mail MichaelJMullen{at}cs.com
Abstract—Flow-mediated dilatation (FMD) of conduit arteries is dependent on an intact endothelium, although the mechanisms are not fully understood. Using high-resolution ultrasound, we examined the role of endothelial mediators in radial artery dilatation in response to transient (short period of reactive hyperemia) and sustained (prolonged period of reactive hyperemia, hand warming, or an incremental infusion of acetylcholine into the distal radial artery) hyperemia. After short episodes of reactive hyperemia, FMD was abolished by local infusion of the nitric oxide synthesis inhibitor NGmonomethyl-L-arginine (5.3±1.2% versus 0.7±0.7%, P<0.001). In contrast, basal vessel diameter and dilatation after prolonged episodes of reactive hyperemia, hand warming, and distal infusion of acetylcholine were not attenuated by nitric oxide synthesis inhibition. Inhibition of cyclooxygenase or local autonomic nervous system blockade also had no effect on FMD. Patients with hypercholesterolemia exhibited reduced FMD in response to transient hyperemia, but the response to sustained hyperemia was normal. These data suggest heterogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus. Dilatation after brief episodes of hyperemia is mediated by release of nitric oxide, whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition. Hypercholesterolemia seems to differentially affect these pathways with impairment of the nitric oxide–dependent pathway and preservation of non nitric oxide–mediated dilatation to sustained flow stimuli.
Key Words: endothelium • nitric oxide • flow-mediated dilatation • vascular physiology
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