This study sought to determine whether afferent feedback associated with peripheral muscle fatigue inhibits central motor drive (CMD) and thereby limits endurance exercise performance. On two separate days, eight men performed constant-load, single-leg knee extensor exercise to exhaustion (85% of peak power) with each leg (Leg1 and Leg2). On another day, the performance test was repeated with one leg (Leg1) and consecutively (within 10 s) with the other/contralateral leg (Leg2-post). Exercise-induced quadriceps fatigue was assessed by reductions in potentiated quadriceps twitch-force from pre- to postexercise (ΔQtw,pot) in response to supramaximal magnetic femoral nerve stimulation. The output from spinal motoneurons, estimated from quadriceps electromyography (iEMG), was used to reflect changes in CMD. Rating of perceived exertion (RPE) was recorded during exercise. Time to exhaustion (∼9.3 min) and exercise-induced ΔQtw,pot (∼51%) were similar in Leg1 and Leg2 (P > 0.5). In the consecutive leg trial, endurance performance of the first leg was similar to that observed during the initial trial (∼9.3 min; P = 0.8); however, time to exhaustion of the consecutively exercising contralateral leg (Leg2-post) was shorter than the initial Leg2 trial (4.7 ± 0.6 vs. 9.2 ± 0.4 min; P < 0.01). Additionally, ΔQtw,pot following Leg2-post was less than Leg2 (33 ± 3 vs 52 ± 3%; P < 0.01). Although the slope of iEMG was similar during Leg2 and Leg2-post, end-exercise iEMG following Leg2-post was 26% lower compared with Leg2 (P < 0.05). Despite a similar rate of rise, RPE was consistently ∼28% higher throughout Leg2-post vs. Leg2 (P < 0.05). In conclusion, this study provides evidence that peripheral fatigue and associated afferent feedback limits the development of peripheral fatigue and compromises endurance exercise performance by inhibiting CMD.

Wray DW, Witman MA, Ives SJ, McDaniel J, Fjeldstad AS, Trinity JD, Conklin JD, Supiano MA, Richardson RS. Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans. Am J Physiol Heart Circ Physiol 300: H1101-H1107, 2011. First published January 7, 2011 doi:10.1152/ajpheart.01115.2010.-In the peripheral circulation, nitric oxide (NO) is released in response to shear stress across vascular endothelial cells. We sought to assess the degree to which NO contributes to exercise-induced vasodilation in the brachial artery (BA) and to determine the potential of this approach to noninvasively evaluate NO bioavailability. In eight young (25 Ϯ 1 yr) healthy volunteers, we used ultrasound Doppler to examine BA vasodilation in response to handgrip exercise (4,8,12,16,20, and 24 kg) with and without endothelial NO synthase blockade [intra-Higher exercise intensities evoked significant BA vasodilation (4 -12%) that was positively correlated with the hyperemic stimulus (r ϭ 0.98 Ϯ 0.003, slope ϭ 0.005 Ϯ 0.001). During NO blockade, BA vasodilation at the highest exercise intensity was reduced by ϳ70% despite similar exercise-induced increases in shear rate (control, ϩ224 Ϯ 30 s Ϫ1 ; L-NMMA, ϩ259 Ϯ 46 s Ϫ1 ). The relationship and slope of BA vasodilation with increasing shear rate was likewise reduced (r ϭ 0.48 Ϯ 0.1, slope ϭ 0.0007 Ϯ 0.0005). We conclude that endothelial NO synthase inhibition with L-NMMA abolishes the relationship between shear stress and BA vasodilation during handgrip exercise, providing clear evidence of NO-dependent vasodilation in this experimental model. These results support this paradigm as a novel and valid approach for a noninvasive assessment of NO-dependent vasodilation in humans. endothelium; endothelial nitric oxide synthase; N G -monomethyl-Larginine MEASUREMENT OF BRACHIAL ARTERY (BA) flow-mediated vasodilation (FMD) following ischemic cuff occlusion, first described by Celermajer et al. (1), has been widely used in recent years as a noninvasive means of evaluating endothelial function in a research setting (10,15,17,20,36). The assessment of endothelial function via FMD has been proposed to represent a functional bioassay for endothelium-derived nitric oxide (NO) bioavailability in humans (7, 16), though there is new evidence challenging the view that FMD is a reliable and selective index of endothelial NO function (23). Earlier work demonstrated a positive correlation between endothelium-dependent vasodilation of the brachial and coronary arteries (32), a finding that has fueled the ongoing interest in a noninvasive evaluation of NO bioactivity in humans.The uncertainty surrounding conventional FMD testing has raised the question of whether a more robust and comprehensive experimental paradigm might be adopted for the noninvasive determination of vascular health. One such approach is dynamic handgrip exercise, first described by Shoemaker et al. (29), which elevates shear stress through the BA and produces a subsequent vasodilation. We ...

Aging is associated with a pro-oxidant state and a decline in endothelial function. Whether acute, enteral antioxidant treatment can reverse this decrement in vascular function is not well known. Flow-mediated vasodilation and reactive hyperemia were evaluated following consumption of either placebo or an oral antioxidant cocktail (Vitamin C, 1000mg; Vitamin E, 600 I.U.; Alpha-lipoic acid, 600 mg) in 87 healthy volunteers (42 young, 25 ± 1 yrs; 45 older, 71 ± 1 yrs) using a double-blind, crossover design. Blood velocity and brachial artery diameter (ultrasound Doppler) were assessed before and after 5-min forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, and Vitamin C were assayed, and plasma nitrate, nitrite, and 3-nitrotyrosine were determined. In the placebo trial, an age-related reduction in brachial artery vasodilation was evident (young: 7.4 ± 0.6 %; older: 5.2 ± 0.4 %). Following antioxidant consumption, flow-mediated vasodilation improved in older subjects (5.2 ± 0.4 %, placebo: 8.2 ± 0.6 %, antioxidant) but declined in the young (7.4 ± 0.6 %, placebo; 5.8 ± 0.6 %, antioxidant). Reactive hyperemia was reduced with age, but antioxidant administration did not alter the response in either group. Together, these data demonstrate that antioxidant consumption acutely restores endothelial function in the elderly, while disrupting normal endothelium-dependent vasodilation in the young, and suggest that this age-related impairment is due, at least in part, to free radicals.