Is Flow-Mediated Dilation Nitric Oxide Mediated?

Abstract

E ndothelial cells synthesize paracrine hormones such as nitric oxide (NO), 1 which have important antiatherogenic properties.2 Early studies in humans that used intra-arterial infusion of endothelial stimulants and inhibitors established that endothelial function is impaired in individuals with cardiovascular diseases and risk factors [3][4][5][6] and that coronary 7,8 and peripheral 9-12 endothelial dysfunction can predict clinical events. In 1992, Celermajer et al 13 introduced an ultrasound technique involving temporary suprasystolic cuff inflation around the limbs and measurement of conduit artery dilation consequent to postischemic hyperemia and an arterial shear stress stimulus. Owing to its relative simplicity, its noninvasive nature, and prognostic research studies that have consistently suggested clinical utility, [14][15][16][17][18][19][20] this so-called flowmediated dilation (FMD) approach has become widely used by both scientists and clinicians.Despite the popularity of the FMD approach, important questions remained unanswered when it was introduced, and the uptake of the technique largely preceded detailed physiological description of underlying mechanisms. In the watershed article of Celermajer and Deanfield, it was reasonably assumed, on the basis of previous animal data, 21,22 that FMD was a flow-and NO-mediated response, despite no evidence being available about its NO dependency. Eventually, the assumption that FMD reflected NO-mediated vascular function was reinforced by physiological experiments that infused NO blockers upstream from an insonated conduit artery and reported that dilator responses to ischemia and shear stress were almost completely abolished. [23][24][25][26] Nonetheless, there have been some well-designed and controlled studies that have been unable to inhibit FMD using NO blockade. 27,28 This disparity in the literature may not only be related to differences in the methodology used to measure FMD, but also to the inclusion of different population groups.Therefore, the aim of this study was to systematically review and meta-analyze the literature relating to crossover studies that have compared FMD under local infusion of saline (FMD saline ) with FMD under local infusion of theto obtain an estimate of the contribution of NO to FMD in human conduit arteries. We used a staged approach and explored the contribution of NO in FMD studies that adopted the standardized approach (ie, using distal cuff placement and ≈5-minute cuff inflation in healthy individuals). Finally, the effect of automated, continuous method of analysis on NO dependency was explored. Abstract-Flow-mediated dilation (FMD) is a noninvasive index of endothelial function and vascular health in humans.Studies examining the role of nitric oxide (NO) are not conclusive. In this article, we quantified the contribution of NO in FMD of conduit arteries and explored the effect of the protocol (ie, distal cuff, ≈5-minute ischemia) and method of analysis (ie, automated and continuous edge detection) on the NO dependenc...

Impact of 2‐Weeks Continuous Increase in Retrograde Shear Stress on Brachial Artery Vasomotor Function in Young and Older Men

“…Before, 30 minutes following, and 2 weeks after sleeve application, endothelium‐dependent,33 mainly NO‐mediated,34 vasodilator function was examined using the flow‐mediated dilation (FMD%). First, subjects rested in the supine position for at least 15 minutes to facilitate baseline assessment of heart rate and blood flow.…”

Impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in older subjects

“…an endothelium-dependent, partly nitric oxide mediated dilation. 27 First, subjects rested supine for a period of at least 15-minutes to facilitate baseline assessment of heart rate and blood flow. Heart rate, systolic, diastolic and mean arterial pressure were measured twice by an experienced researcher from the left brachial artery in supine subjects using a manual sphygmomanometer.…”

Oral Administration of Glucosamine Improves Vascular Endothelial Function by Modulating Intracellular Redox State

“…But a recent meta-analysis reveals that up to 72% of the FMD is mediated by nitric oxide in healthy subjects. 36) Therefore, glucosamine administration attributes to the improvement of FMD, at least in part.…”