The phenomenon of flow-mediated dilation (FMD) relevant to this debate describes the vasodilation in a conduit vessel in response to elevations in flow-associated shear stress. Nitric oxide (NO) is thought to play a key role in vascular health due to its established vasoprotective characteristics (for review, see Ref. 8). Because NO is one of the substances produced by the vascular endothelium in response to elevations in flow-associated shear stress (2), considerable clinical interest has focused on noninvasive assessment of FMD for evaluating NO-specific endothelial function in humans.

Celermajer et. al (4) in 1992 were the first to examine FMD induced by elevated forearm conduit vessel blood flow velocity after ischemia-induced downstream vasodilation [reactive hyperemia (RH)] to assess FMD in groups at risk for atherosclerosis and observed a blunted response. Since then, numerous studies assessing FMD in various pathologies and in response to various therapeutic interventions have been conducted. A blunting of the FMD response relative to healthy controls is taken to represent endothelial dysfunction. With regard to NO, Joannides et al.(17) in 1995 were the first to examine the NO contribution to RH-induced FMD in humans and found that NO blockade completely abolished FMD. Their concluding statement was “… the present investigation demonstrates that NO is essential for flow mediated dilatation of human radial arteries in vivo. Thus this test can be used as a reliable noninvasive estimate of the capacity of human endothelial cells to release NO…” The common clinical view now, as stated in the recent technique report by the International Brachial Artery Reactivity Task Force in 2002 (6), is that vascular endothelial NO production accounts for FMD, and the primary citation supporting this is the above-mentioned Joannides et al.(17) paper.