Branton G. Walker

Ageing reduces the compensatory vasodilatation during hypoxic exercise: the role of nitric oxide

Non‐technical summary  In young healthy humans, the combination of exercise and hypoxia produces a compensatory vasodilatation to ensure the maintenance of oxygen to the active muscles. We have previously demonstrated that nitric oxide (NO) is a major factor responsible for the compensatory vasodilatation. In this paper we show that the compensatory vasodilator response to hypoxic exercise is attenuated in older adults due to less NO signalling. These findings provide important information on the impact of ageing and the role of NO in the regulation of skeletal muscle blood flow during conditions of reduced oxygen availability.

Contribution of nitric oxide in the contraction-induced rapid vasodilation in young and older adults

We tested the hypothesis that reduced nitric oxide (NO) bioavailability contributes to the attenuated peak and total vasodilation following single-muscle contractions in older adults. Young (n = 10; 24 ± 2 yr) and older (n = 10; 67 ± 2 yr) adults performed single forearm contractions at 10, 20, and 40% of maximum during saline infusion (control) and NO synthase (NOS) inhibition via N(G)-monomethyl-l-arginine. Brachial artery diameters and velocities were measured using Doppler ultrasound and forearm vascular conductance (FVC; in ml·min(-1)·100 mmHg(-1)) was calculated from blood flow (ml/min) and blood pressure (mmHg). Peak and total vasodilator responses [change (Δ) in FVC from baseline] were attenuated in older adults at all intensities (P < 0.05). NOS inhibition reduced the peak ΔFVC at 10% (88 ± 12 vs. 52 ± 9 ml·min(-1)·100 mmHg(-1)), 20% (125 ± 13 vs. 83 ± 13 ml·min(-1)·100 mmHg(-1)), and 40% (207 ± 26 vs. 133 ± 20 ml·min(-1)·100 mmHg(-1)) in young subjects, (P < 0.05 for all) and in older adults at 10% (59 ± 5 vs. 47 ± 7 ml·min(-1)·100 mmHg(-1), P < 0.05) and 20% (88 ± 9 vs. 68 ± 9 ml·min(-1)·100 mmHg(-1), P < 0.05), but not 40% (128 ± 12 vs. 105 ± 11 ml·min(-1)·100 mmHg(-1), P = 0.11). The relative (%) reduction in peak ΔFVC due to NOS inhibition was greater in young vs. older adults at 20% (-36 ± 5 vs. -23 ± 5%, P < 0.05) and 40% (-35 ± 6 vs. -16 ± 7%, P < 0.05). The reduction in the total vasodilator response (area under the curve) with NOS inhibition was also greater in young vs. older adults at all intensities. Our data suggest that contraction-induced rapid vasodilation is mediated in part by NO, and that the contribution of NO is greater in young adults.

Effect of vitamin C on hyperoxia-induced vasoconstriction in exercising skeletal muscle

Hyperoxia can cause substantial reductions in peripheral and coronary blood flow at rest and during exercise, which may be caused by reactive oxygen species (ROS) generated during hyperoxia. The aim of this study was to investigate the role of ROS in hyperoxia-induced reductions in skeletal muscle blood flow during forearm exercise. We hypothesized that infusion of vitamin C would abolish the effects of hyperoxia on the forearm blood flow (FBF) responses to exercise. Twelve young healthy adults performed rhythmic forearm handgrip exercise (10% of maximum voluntary contraction for 5 min) during normoxia and hyperoxia. For each condition, two trials were conducted with intra-arterial administration of saline or vitamin C. FBF was measured using Doppler ultrasound. During hyperoxia with saline, FBF and forearm vascular conductance (FVC) were 86.3 ± 5.1 and 86.8 ± 5.2%, respectively, of the normoxic values (100%) (P < 0.05). During vitamin C, hyperoxic FBF and FVC responses were 90.9 ± 4.2 and 90.9 ± 4.1%, respectively, of the normoxic values (P = 0.57 and 0.59). Subjects were then divided into three subgroups based on their percent decrease in FBF (>20, 10-20, and <10%) during hyperoxia. In the subgroup that demonstrated the greatest hyperoxia-induced changes (>20%), FBF and FVC during hyperoxia were 67.1 ± 4.0 and 66.8 ± 3.6%, respectively, of the normoxic values. Vitamin C abolished these effects on FBF and FVC with values that were 102.0 ± 5.2 and 100.8 ± 6.1%, respectively. However, vitamin C had no effect in the other two subgroups. This analysis is consistent with the idea that ROS generation blunts the FBF responses to exercise in the subjects most affected by hyperoxia.