Keeping the juices flowing with age: vitamin C and exercise hyperaemia

In a recent issue of The Journal of Physiology Kirby and colleagues (Kirby et al. 2009) demonstrate that acute brachial artery administration of vitamin C enhances the steady-state blood flow responses to rhythmic hand gripping in older humans. They showed that vitamin C administration both before and during hand gripping caused a marked (30%) increase in forearm vascular conductance and blood flow during 10% rhythmic forearm exercise. By contrast, vitamin C does not restore or improve vasodilator response to a single contraction which is blunted by ageing both with and without vitamin C. The authors discuss their findings and how they relate to three well-known previous observations: First, it is known that acute vitamin C administration via the brachial artery augments acetylcholine-mediated vasodilatation probably as a result of either increased NO production or increased NO bioavailability; second, while endothelial-mediated vasodilating substances clearly contribute to exercise hyperaemia in young people, their contribution is clearly blunted in older subjects; and third, the improvement in vasodilatation in response to vitamin C both at rest and during exercise was specific to the endothelium and not due to an improvement in smooth muscle cell responsiveness in the forearm vessels (Eskurza et al. 2004, 2005; Schrage et al. 2007). It is also interesting to speculate that the blunted endothelial contribution to exercise hyperaemia also limits functional sympatholysis and makes it ‘easier’ for the high levels of sympathetic nerve traffic seen in older humans to restrain blood flow to active muscles (Koch et al. 2003; Dinenno et al. 2005). Based on the above findings, several important questions with a clinical bent emerge. First, can these observations be applied to whole-body exercise and will dietary supplementation with vitamin C, other antioxidants, or perhaps BH-4 be useful to improve exercise capacity in sedentary older humans (Katusic et al. 2009)?Second, might these interventions improve exercise capacity in middle-aged and older subjects with conditions like mild congestive heart failure, hypertension and peripheral artery disease? All are associated with blunted vasodilator responses during exercise, deficient endothelial-mediated vasodilatation, and increased sympathetic outflow. Together these factors may operate in a way to further limit exercise capacity, make exercise training more difficult, and thus limit the ability of patient groups who can clearly benefit from physical activity to take part in it (Drexler & Hornig, 1996; Green et al. 2004; Zhao et al. 2006). A third important question is whether or not the observations seen in the forearm of relatively sedentary older subjects can be reversed by training. Long-term endurance exercise training and even short-term interventions focusing on ‘adult fitness’-style walking programmes have been shown to either maintain endothelial function at levels seen in younger subjects or improve it with just a few months of training (DeSouza et al. 2000; Green et al. 2004). Additionally, this training appears to have effects on both the vascular beds subject to the training and also systemic effects (i.e. the arms of subjects who have undergone leg training). Fourth, what role might diet play to improve blood flow responses to exercise in older humans? A diet with limited meat that is high in fruits, vegetables and unsaturated fat appears protective against a variety of age-related changes in cardiovascular function (Fraser & Shavlik, 2001). Many of these protective effects are thought to work via the vascular endothelium. Will these population-based effects also be seen in exercising skeletal muscle and be associated with improved exercise capacity in ageing humans?Finally, while vitamin C did not improve the rapid vasodilator responses seen after a single contraction in older subjects, will exercise training? In summary, Kirby and colleagues have made a provocative finding. The question now is whether exercise training, habitual physical activity, diet, or supplements improve blood flow to contracting muscles in healthy and sedentary older subjects and individuals with age-related cardiovascular conditions. Additionally, will training or habitual physical activity also preserve the normal rapid vasodilator responses seen at the onset of exercise? The observations made in this paper and the questions emanating from it have clear therapeutic implications for health preservation in older humans, and health restoration in patients with hypertension, heart failure, and peripheral vascular disease. Older humans who ‘follow the guidelines’ related to exercise and diet live very long and very productive lives (Fraser & Shavlik, 2001). Will answering the questions raised by the Kirby paper help us understand why, and develop therapeutic strategies that can be used in diseases caused not by deficient levels of vitamin C, but by deficient lifestyles?