Crecelius AR, Kirby BS, Voyles WF, Dinenno FA. Nitric oxide, but not vasodilating prostaglandins, contributes to the improvement of exercise hyperemia via ascorbic acid in healthy older adults. Am J Physiol Heart Circ Physiol 299: H1633-H1641, 2010. First published September 3, 2010; doi:10.1152/ajpheart.00614.2010.-Acute ascorbic acid (AA) administration increases muscle blood flow during dynamic exercise in older adults, and this is associated with improved endothelium-dependent vasodilation. We directly tested the hypothesis that increase in muscle blood flow during AA administration is mediated via endothelium-derived vasodilators nitric oxide (NO) and prostaglandins (PGs). In 14 healthy older adults (64 Ϯ 3 yr), we measured forearm blood flow (FBF; Doppler ultrasound) during rhythmic handgrip exercise at 10% maximum voluntary contraction. After 5-min steady-state exercise with saline, AA was infused via brachial artery catheter for 10 min during continued exercise, and this increased FBF ϳ25% from 132 Ϯ 16 to 165 Ϯ 20 ml/min (P Ͻ 0.05). AA was infused for the remainder of the study. Next, subjects performed a 15-min exercise bout in which AA ϩ saline was infused for 5 min, followed by 5 min of the nitric oxide synthase (NOS) inhibitor N G -monomethyl-L-arginine (L-NMMA) and then 5 min of the cyclooxygenase inhibitor ketorolac (group 1). The order of inhibition was reversed in eight subjects (group 2). In group 1, independent NOS inhibition reduced steady-state FBF by ϳ20% (P Ͻ 0.05), and subsequent PG inhibition had no impact on FBF (⌬ 3 Ϯ 5%). Similarly, in group 2, independent PG inhibition had little effect on FBF (⌬ Ϫ4 Ϯ 4%), whereas subsequent NO inhibition significantly decreased FBF by ϳ20% (P Ͻ 0.05). In a subgroup of five subjects, we inhibited NO and PG synthesis before AA administration. In these subjects, there was a minimal nonsignificant improvement in FBF with AA infusion (⌬ 7 Ϯ 3%; P ϭ nonsignificant vs. zero). Together, our data indicate that the increase in muscle blood flow during dynamic exercise with acute AA administration in older adults is mediated primarily via an increase in the bioavailability of NO derived from the NOS pathway. blood flow; aging; muscle contractions THE REGULATION OF BLOOD FLOW and oxygen delivery to contracting muscle is a complex response that involves mechanical factors, the sympathetic nervous system, and local metabolic and endothelium-derived substances that can influence vascular tone (28). In aging humans, an imbalance occurs in these regulatory mechanisms that typically results in impaired vasodilation and attenuated muscle blood flow during exercise (17,19,25,26). Investigators have hypothesized that impaired endothelial vasodilator function contributes to the age-related impairment in muscle blood flow during exercise (8,27). Recently, our laboratory demonstrated (17) that improving endothelium-dependent vasodilation via the potent antioxidant ascorbic acid also improved muscle blood flow during rhythmic handgrip exercise in older adults, providing the...