The associated decrease in intracellular pH is a factor leading to muscle fatigue [23, 24]. Therefore, during maximal exertion blood flow is needed not only for oxygen supply to support continued oxidative phosphorylation, but also for H+ removal for muscle pH regulation. It would seem that exogenous ATP would likely have a greater impact on the muscles’ ability to perform fatiguing exercise by increasing substrate availability to the muscle and/or RG7420 solubility dmso facilitating waste A-1210477 concentration product removal through increased blood flow through the muscle tissues. Both ATP and adenosine can act through purinergic receptors in endothelial
smooth muscle of the vascular system resulting in vasodilation and increased blood flow [14, 15, 25]. A study by Gonzalez-Alonso showed that intra-arterial infusion of ATP was associated with vasodilation and increased blood flow with a significant reduction in venous ATP levels in the non-exercising limb suggesting utilization of ATP or metabolites . These
observations were confirmed by Calbet et al. who hypothesized Selleck XAV939 that increased delivery of ATP would affect non-exercising vasoconstrictive muscle tissue . These are most likely due to activation of purinergic receptors affecting blood flow . Furthermore, exogenous adenosine administration results in vasodilation  and increased glucose and O2 uptake by muscle which provide for an increased substrate pool . The ATP used in the present study was not enterically coated and was fed encapsulated as the disodium salt. The sodium salt would have
provided buffering of the ATP through the stomach and the ATP itself should have been metabolically Thalidomide available as soon as it reached the proximal duodenum, which has been shown to be the most biologically active site for ATP metabolism and/or absorption . In France, this chemical form of ATP is approved as a drug for lower back pain [27, 28]. One proposed mechanism of action is through improved oxygenation of the muscle, which could be of similar benefit during exhaustive exercise. Other effects of ATP or its metabolites could also indirectly impact work performance as ATP has immunomodulatory effects , and inotropic effects on cardiac muscle [30, 31]. Oral administration of ATP to rabbits for 14 days results in systemic effects through a reduction in peripheral vascular resistance, improvement of cardiac output, reduction of lung resistance, and increased arterial PaO2. A study in humans demonstrated that interstitial infusion of adenosine in muscle induced nitric oxide formation in skeletal muscle and nitric oxide and prostacyclin formation in microvascular endothelial cells . Alternatively, the effects of cbvexogenously administered ATP may also be due to the associated increase in plasma uric acid, which has been proposed to act as an anti-oxidant [33, 34].