Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans

Abstract

Flow-mediated dilatation (FMD) of the brachial and radial arteries is an important research tool for assessment of endothelial function in vivo, and is nitric oxide (NO) dependent. The leg skeletal muscle vascular bed is an important territory for studies in exercise physiology. However, the role of endothelial NO in the FMD response of lower limb arteries has never been investigated. The purpose of this study was to examine the contribution of NO to FMD in the superficial femoral artery in healthy subjects. Since physical inactivity may affect endothelial function, and therefore NO availability, spinal cord-injured (SCI) individuals were included as a model of extreme deconditioning. In eight healthy men (34 +/- 13 years) and six SCI individuals (37 +/- 10 years), the 5 min FMD response in the superficial femoral artery was assessed by echo-Doppler, both during infusion of saline and during infusion of the NO synthase blocker N(G)-monomethyl-L-arginine (L-NMMA). In a subset of the controls (n = 6), the 10 min FMD response was also examined using the same procedure. The 5 min FMD response in controls (4.2 +/- 0.3%) was significantly diminished during L-NMMA infusion (1.0 +/- 0.2%, P < 0.001). In SCI, L-NMMA also significantly decreased the FMD response (from 8.2 +/- 0.4% during saline to 2.4 +/- 0.5% during L-NMMA infusion). The hyperaemic flow response during the first 45 s after cuff deflation was lower in both groups during infusion of L-NMMA, but the effect of L-NMMA on FMD persisted in both groups after correction for the shear stress stimulus. The 10 min FMD was not affected by L-NMMA (saline: 5.4 +/- 1.6%, L-NMMA: 5.6 +/- 1.5%). Superficial femoral artery FMD in response to distal arterial occlusion for a period of 5 min is predominantly mediated by NO in healthy men and in the extremely deconditioned legs of SCI individuals.

Figure 1. Schematic overview of the invasive study protocol

RH, reactive hyperaemia.

Figure 2. Baseline and post-ischaemic blood flow, mean wall shear rate and superficial femoral diameter

Average baseline and post-ischaemic blood flow (A) and mean wall shear rate (B) during the first 45 s of reactive hyperaemia, and (C) percentage change in superficial femoral diameter during the post-ischaemic period from minute 1 to minute 5 in controls (squares) and SCI individuals (circles) during infusion of saline (open) or l-NMMA (filled). Data are presented as mean +s.e.m. The brackets represent the ANOVA results. *Significant time effect for both groups (P < 0.05, 2-way ANOVA). †Significant interaction for condition (saline or l-NMMA) × time for both groups separately. ‡Significant between group effect (P < 0.05, 2-way ANOVA). During infusion of l-NMMA no time effect in superficial femoral artery diameter was observed in both groups (1-way ANOVA).

Figure 3. FMD

FMD presented as: A, maximal relative change in superficial femoral artery diameter, and B, the corrected FMD for the area-under-the-curve of the post-ischaemic mean wall shear rate (AUC-MWSR) in controls and SCI individuals during infusion of saline (filled bars) or l-NMMA (open bars). Results are presented as mean +s.e.m.*Significantly different between saline and l-NMMA at P < 0.05 (Student/s t test).

Figure 4. Relative change in the superficial femoral artery

Relative change in the superficial femoral artery during a 5 and 10 min FMD procedure, under infusion of saline (filled bars) or l-NMMA (open bars) in a subpopulation of the original group of healthy able-bodied control subjects (n = 6). A paired t test is used to compare the diameter change to the situation with saline and l-NMMA infusion, but also between the 5 and 10 min FMD. Error bars represent s.e.m.