Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion

Abstract

Pyke K, Green DJ, Weisbrod C, Best M, Dembo L, O'Driscoll G, Tschakovsky ME. Nitric oxide is not obligatory for radial artery flowmediated dilation following release of 5 or 10 min distal occlusion. Am J Physiol Heart Circ Physiol 298: H119 -H126, 2010. First published October 30, 2009 doi:10.1152/ajpheart.00571.2009.-This study investigated the nitric oxide (NO) dependence of radial artery (RA) flowmediated dilation (FMD) in response to three different reactive hyperemia (RH) shear stimulus profiles. Ten healthy males underwent the following three RH trials: 1) 5 min occlusion (5 trial), 2) 10 min occlusion (10 trial), and 3) 10 min occlusion with cuff reinflation at 30 s (10 -30 trial). Trials were performed during saline infusion and repeated during N G -monomethyl-L-arginine (L-NMMA) infusion in the brachial artery. RA blood flow velocity was measured with Doppler ultrasound, and B-mode RA images were analyzed using automated edge detection software. Shear rate estimation of shear stress was calculated as the blood flow velocity/vessel diameter. L-NMMA decreased baseline vascular conductance by 35%. L-NMMA infusion did not affect the peak shear rate stimulus (P ϭ 0.681) or the area under the curve (AUC) of shear rate to peak FMD (P ϭ 0.088). The AUC was significantly larger in the 10 trial vs. the 10 -30 or 5 trial (P Ͻ 0.001). Although percent FMD (%change in diameter) in the 10 trial was larger than that in the 5 trial (P ϭ 0.035), there was no significant difference in %FMD between the saline and L-NMMA conditions in any trial: 5 trial, 5.62 Ϯ 1.48 vs. 5.63 Ϯ 1.27%; 10 trial, 9.07 Ϯ 1.16 vs. 11.22 Ϯ 2.21%; 10 -30 trial, 6.52 Ϯ 1.43 vs. 7.98 Ϯ 1.51% for saline and L-NMMA, respectively (P ϭ 0.158). We conclude the following: 1) RH following 10 min of occlusion results in an enhanced stimulus and %FMD compared with 5 min of occlusion. 2) When the occlusion cuff is reinflated 30 s postrelease of a 10 min occlusion, it does not result in an enhanced %FMD compared with that which results from RH following 5 min of occlusion.3) The lack of effect of L-NMMA on FMD suggests that NO may not be obligatory for radial artery FMD in response to either 5 or 10 min of occlusion in healthy volunteers. nitric oxide; endothelium; shear stress IN HEALTHY ARTERIES, an increase in blood flow (and shear stress) results in endothelial-dependent flow-mediated dilation (FMD) (29,32,41). FMD can therefore serve as an index of endothelial function and provide insight regarding vascular health (42). Originally published by Celermajer et al. (8), the test most commonly performed in humans increases shear stress in conduit arteries (e.g., the brachial, radial, femoral, or popliteal) via reactive hyperemia following the release of temporary limb ischemia (8). A "standard" technique has emerged that stipulates a 5-min cuff occlusion duration, a cuff position distal to the site of conduit artery diameter measurement, and the absence of exercise performed during occlusion (31). The primary reason for these constraints is the desire to cre...

Is Flow-Mediated Dilation Nitric Oxide Mediated?

“…[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).…”

“…[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.…”

There^|^rsquo;s More to Flow-Mediated Dilation Than Nitric Oxide

“…PGI2 and Relative Contribution to Flow-Mediated Dilation Doshi et al 94) found that administration of NOS inhibitor N G -monomethyl-L-arginine (L-NMMA) completely abolished FMD of the brachial artery following 5 minutes of wrist cuff occlusion, with no difference in the hyperemic stimulus; however, L-NMMA does not completely block the FMD response when the occlusion cuff is placed on the upper arm 94,95) (see Table 1). Similarly, L-NMMA does not completely abolish FMD in the radial 11,27,28,[96][97][98][99][100][101] and femoral arteries 12) . The relative importance of NO to FMD may also be altered when conducting this test on patients with a number of diseased states, such as dystonia 26) , chronic heart failure 27) or hypertension 28) (see Table 2).…”

“…Furthermore, studies have shown that the proportional contribution of NO to FMD is diminished when conduit arteries are exposed to prolonged increases in shear stress. This has been demonstrated via the use of occlusion periods greater than 5 minutes, or through local hand warming 98) .…”

“…Pyke et al 98) Fischer et al 99) Mullen et al 100) Pyke et al 98) Seddon et al 101) Mullen et al 100) Hornig et al…”