Non-technical summary We investigated the role of thin fibre muscle afferents in the circulatory response to exercise in humans. The results not only document the importance of continuous afferent feedback from working human skeletal muscle to achieve appropriate haemodynamic and ventilatory responses to exercise but also suggest that the relative contribution of this mechanism is larger than traditionally accepted. AbstractWe investigated the role of skeletal muscle afferent feedback in circulatory control during rhythmic exercise in humans. Nine healthy males performed single leg knee-extensor exercise (15/30/45 watts, 3 min each) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. Cardiac output and femoral blood flow were determined, and femoral arterial/venous blood samples were collected during the final minute of each workload. To rule out cephalad migration of fentanyl to the brainstem, we documented unchanged resting ventilatory responses to different levels of hypercapnia. There were no haemodynamic differences between conditions at rest. However, during exercise cardiac output was ∼20% lower with fentanyl blockade compared to control (P < 0.05), secondary to a 6% and 13% reduction in heart rate and stroke volume, respectively. Throughout exercise mean arterial pressure (MAP) was reduced by 7% (P < 0.01) which is likely to have contributed to the 15% fall in femoral blood flow. However, MAP was not completely responsible for this peripheral haemodynamic change as vascular conductance was also attenuated (∼9%). Evidence of increasing noradrenaline spillover (P = 0.09) implicated an elevation in sympathetic outflow in this response. The attenuated femoral blood flow during exercise with fentanyl was associated with a 17% reduction in leg O 2 delivery (P < 0.01) and a concomitant rise in the arteriovenous O 2 difference (4-9%), but leg O 2 consumption remained 7-13% lower than control (P < 0.05). Our findings reveal an essential contribution of continuous muscle afferent feedback to ensure the appropriate haemodynamic and ultimately metabolic response to rhythmic exercise in humans. Abbreviations FBF, femoral blood flow; HR, heart rate; LVC, leg vascular conductance; MAP, mean arterial pressure; NA, noradrenaline; SV, stroke volume.
Objective: To determine (1) whether obese older adults had higher prevalence of falls and ambulatory stumbling, impaired balance and lower health-related quality of life (HRQL) than their normal weight counterparts, and (2) whether the falls and balance measures were associated with HRQL in obese adults. Methods:Subjects who had a body mass index (BMI) greater than 30 kg/m 2 were classified into an obese group (n = 128) while those with BMI between 18.5 and 24.9 kg/m 2 were included into a normal weight group (n = 88). Functional tests were performed to assess balance, and questionnaires were administered to assess history of falls, ambulatory stumbling, and HRQL. Results:The obese group reported a higher prevalence of falls (27% vs. 15%), and ambulatory stumbling (32% vs. 14%) than the normal weight group. Furthermore, the obese group had lower HRQL, (p ≤ 0.05) for physical function (63 ± 27 vs. 75 ± 26; mean ± SD), role-physical (59 ± 40 vs. 74 ± 37), vitality (58 ± 23 vs. 66 ± 20), bodily pain (62 ± 25 vs. 74 ± 21) and general health (64 ± 19 vs. 70 ± 18). In the obese group, a history of falls was related (p ≤ 0.05) to lower scores in 4 domains of HRQL, and ambulatory stumbling was related (p ≤ 0.01) to 7 domains. Conclusion:In middle-aged and older adults, obesity was associated with a higher prevalence of falls and stumbling during ambulation, as well as lower values in multiple domains of HRQL. Furthermore, a history of falls and ambulatory stumbling were related to lower measures of HRQL in obese adults.
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 ...
Background: Physical activity is associated with health-related quality of life (HRQL) in clinical populations, but less is known whether this relationship exists in older men and women who are healthy. Thus, this study determined if physical activity was related to HRQL in apparently healthy, older subjects.
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.
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