Endothelium‐dependent vasodilatation and exercise hyperaemia in ageing humans: impact of acute ascorbic acid administration

Abstract

Age-related increases in oxidative stress impair endothelium-dependent vasodilatation in humans, leading to the speculation that endothelial dysfunction contributes to impaired muscle blood flow and vascular control during exercise in older adults. We directly tested this hypothesis in 14 young (22 ± 1 years) and 14 healthy older men and women (65 ± 2 years). We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) responses to single muscle contractions at 10, 20 and 40% maximum voluntary contraction (MVC) before and during ascorbic acid (AA) infusion, and we also determined the effects of AA on muscle blood flow during mild (10% MVC) continuous rhythmic handgrip exercise. For single contractions, the peak rapid hyperaemic responses to all contraction intensities were impaired ∼45% in the older adults (all P < 0.05), and AA infusion did not impact the responses in either age group. For the rhythmic exercise trial, FBF (∼28%) and FVC (∼31%) were lower (P = 0.06 and 0.05) in older versus young adults after 5 min of steady-state exercise with saline. Subsequently, AA was infused via brachial artery catheter for 10 min during continued exercise. AA administration did not significantly influence FBF or FVC in young adults (1-3%; P = 0.24-0.59), whereas FBF increased 34 ± 7% in older adults at end-exercise, and this was due to an increase in FVC (32 ± 7%; both P < 0.05). This increase in FBF and FVC during exercise in older adults was associated with improvements in vasodilator responses to acetylcholine (ACh; endothelium dependent) but not sodium nitroprusside (SNP; endothelium independent). AA had no effect on ACh or SNP responses in the young. We conclude that acute AA administration does not impact the observed age-related impairment in the rapid hyperaemic response to brief muscle contractions in humans; however, it does significantly increase muscle blood flow during continuous dynamic exercise in older adults, and this is probably due (in part) to an improvement in endothelium-dependent vasodilatation.

Reduced muscle oxidative capacity is independent of O2 availability in elderly people

“…Indeed, while hyperoxia enhanced O 2 availability by increasing blood O 2 content, antioxidant administration induced an increase in muscle blood flow by enhanced scavenging of free radicals and a subsequent increase in nitric oxide (NO) bioavailability in the elderly subjects (Wray et al 2011). Although such an intervention has consistently been documented to increase muscle blood flow in old sedentary subjects by restoring endothelium-dependent vasodilation (Donato et al 2006;Kirby et al 2009), an acute increase in NO bioavailability has also been recognized to decrease O 2 cost (Larsen et al 2010) and improve mitochondrial efficiency (Larsen et al 2011). Therefore, while an improved O 2 supply may contribute to some extent to the faster PCr recovery in the study of Wray et al (2009b), other factors related to mitochondrial function could also play a role when antioxidant administration alters NO bioavailability.…”

Nitric oxide, but not vasodilating prostaglandins, contributes to the improvement of exercise hyperemia via ascorbic acid in healthy older adults

“…With this information as background, the purpose of the present investigation was to extend our original observations (17) and directly test the hypothesis that the ascorbic acidmediated improvement in muscle blood flow during exercise in older humans is primarily via a NO and PG mechanism. To test this hypothesis, we measured forearm hemodynamics (Doppler ultrasound) during rhythmic forearm handgrip exercise before and during ascorbic acid infusion followed by independent and combined inhibition of NO and PG synthesis in healthy older humans.…”

“…Related to vasodilating PGs, COX inhibition during exercise in aging humans has essentially no impact on FBF (29), whereas in young adults inhibition of PG synthesis results in a transient ϳ12% reduction in FBF during rhythmic handgrip exercise (30). Together, these data indicate that older adults demonstrate an attenuated contribution of endothelial vasodilatory pathways (e.g., NO and PGs) to exercise hyperemia compared with young healthy humans.In older humans, ascorbic acid infusion has been shown to improve endothelial vasodilator function in response to both pharmacological (acetylcholine) and physiological (flow mediated) stimuli (9, 17, 33), whereas it has no effect in young healthy subjects (17,32,33). In the case of an acetylcholine stimulus, the improvement due to ascorbic acid was directly related to a restoration of NO bioavailability (33).…”

“…In older humans, ascorbic acid infusion has been shown to improve endothelial vasodilator function in response to both pharmacological (acetylcholine) and physiological (flow mediated) stimuli (9, 17, 33), whereas it has no effect in young healthy subjects (17,32,33). In the case of an acetylcholine stimulus, the improvement due to ascorbic acid was directly related to a restoration of NO bioavailability (33).…”

“…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).…”