Ascorbic Acid Improves Brachial Artery Vasodilation during Progressive Handgrip Exercise in the Elderly through a Nitric Oxide-Mediated Mechanism
Aging, endothelium, l-NMMA, vascular function
The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.
American Journal of Physiology - Heart and Circulatory Physiology
Trinity JD, Wray DW, Witman MA, Layec G, Barrett-O'Keefe Z, Ives SJ, Conklin JD, Reese V, Zhao J, Richardson RS. Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism. Am J Physiol Heart Circ Physiol. 2016 Mar 15;310(6):H765-74. doi: 10.1152/ajpheart.00817.2015. Epub 2016 Jan 22. PubMed PMID: 26801312.