S were lower in the cuffed arm versus the control arm (arm main effect: P < 0.05) and without differences between cuff pressures (20 mmHg: 5.7 ?2.2 ; 40 mmHg: 4.7 ?1.3 ; 60 mmHg: 5.4 ?2.4 ) (P > 0.05). Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P < 0.05) but were not different (control: 7.1 ?3.5 vs. cuffed: 6.6 ?3.3 ) (P > 0.05). Conclusions: These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose esponse in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and retrograde shear during exercise on FMD. Keywords: Antegrade, Antioxidant, Oxidative stress, Supine cycle ergometer* Correspondence: [email protected] 1 Department of Kinesiology, Indiana University, Bloomington, IN, USA 4 Department of Anesthesiology, 200 First Street SW, SMH, Joseph 4-184, Rochester, MN 55905, USA Full list of author information is available at the end of the article?2012 Johnson et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Johnson et al. Cardiovascular Ultrasound 2012, 10:34 http://www.cardiovascularultrasound.com/content/10/1/Page 2 ofBackground Improvements in recognized traditional and novel risk factors account for approximately 59 of the benefits associated with exercise which PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25447644 leaves a large portion of the exercise-induced reduction of disease risk unexplained [1]. Exercise provides direct beneficial effects to the vasculature which may contribute to the unexplained cardiovascular disease risk reduction [2]. Data obtained from animals and humans demonstrate that exercise produces an increased superoxide dismutase expression/ activity [3], improved endothelial nitric oxide synthase (eNOS) expression and phosphorylation [4], enhanced acetylcholine-induced vasomotor function [5], and a reduction in pro-oxidant enzymes [3,6]. These beneficial effects on the endothelium may be a result of exerciseinduced shear stress, which has been postulated to directly contribute to the improved function of the endothelium following exercise [2,7]. Oscillatory and retrograde shear stress appear to adversely influence endothelial cells in vitro and these effects have been studied extensively. Retrograde and oscillatory shear stress profiles increase mRNA of adhesion FCCP web molecules [8,9], endothelin-1 [10], monocyte chemotactic protein 1 [9,11], gp91phox [11], Nox4 and reactive oxygen species [11,12] and decrease eNOS mRNA [11]. These shear patterns also stimulate mitochondrial production of reactive oxygen species [13]. Superoxide anions generated through these pathways also rapidly react with NO to form peroxynitrite [14], which uncouples eNOS by oxidizing tetrahydrobiopterin (BH4). Uncoupled eNOS further increases superoxide anion production leading to a vicious cycle of reactive oxygen species production [15] and decreased NO bioavailability [15]. Oxidative stress in endothelial cells is reduced and eNOS function is preserved when the antioxidant vi.
