Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide

Abstract

Flow-mediated dilatation (FMD) of the brachial artery assessed by high-resolution ultrasound is widely used to measure endothelial function. However, the technique is not standardized, with different groups using occlusion of either the wrist or the upper arm to induce increased blood flow. The validity of the test as a marker of endothelial function rests on the assumption that the dilatation observed is endothelium-dependent and mediated by nitric oxide (NO). We sought to compare the NO component of brachial artery dilatation observed following wrist or upper arm occlusion. Dilatation was assessed before and during intra-arterial infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) following occlusion of (i) the wrist (distal to ultrasound probe) and (ii) the upper arm (proximal to ultrasound probe) for 5 min in ten healthy males. Dilatation was significantly greater after upper arm occlusion (upper arm, 11.62+/-3.17%; wrist, 7.25+/-2.49%; P=0.003). During L-NMMA infusion, dilatation after wrist occlusion was abolished (from 7.25+/-2.49% to 0.16+/-2.24%; P<0.001), whereas dilatation after upper arm occlusion was only partially attenuated (from 11.62+/-3.17% to 7.51+/-2.34%; P=0.006). The peak flow stimulus was similar after wrist and upper arm occlusion. We conclude that dilatation following upper arm occlusion is greater than that observed after wrist occlusion, despite a similar peak flow stimulus. L-NMMA infusion revealed that FMD following wrist occlusion is mediated exclusively by NO, while dilatation following upper arm occlusion comprises a substantial component not mediated by NO, most probably related to tissue ischaemia around the brachial artery. FMD following wrist occlusion may be a more valid marker of endothelial function than dilatation following upper arm occlusion.

Effects of n–3 fatty acids on macro- and microvascular function in subjects with type 2 diabetes mellitus

“…Whereas FMD is predominantly mediated by nitric oxide (NO) (33), the microcirculation is largely independent of NO-mediated regulation and is subject to prostaglandin (34) and nonendotheliumdependent pathways (35).…”

Diurnal Variation in Vascular Function: Role of Sleep

“…The primary outcome variable of the current study was endothelium-dependent, nitric oxide-mediated vasodilation, and we employed the most appropriate FMD methodology on young healthy individuals to suggest a largely NO-mediated response (Doshi et al, 2001;Joannides et al, 1995). Vascular smooth muscle Diurnal Variation in FMD  function (i.e., endothelium-independent vasodilatation) was not measured; however, we are confident that it is not likely to be a significant factor, since previous studies have reported no diurnal variation in endothelium-independent vasodilator function (Gaenzer et al, 2000;Kawano et al, 2002).…”

The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction

“…In order to minimise the confounding effects of the vasoactive drugs, we maintained the same medications throughout the baseline and follow-up examination, and thus we believe that it did not affect the validity of our study. Second, the upper arm occlusion method may be confounded by ischaemia of the brachial artery and be less sensitive to endothelial dysfunction than the forearm occlusion method,18 19 although it was also reported that upper arm occlusion elicited a greater percentage change in the diameter of the brachial artery and thus better separated subjects with and without coronary risk factors 20. Third, a recent study demonstrated significant individual variation in the time course of FMD and thus measurement at a single fixed time point may reduce the discriminatory power of FMD testing 21.…”