This report was presented at The Journal of Physiology Symposium on Blood flow regulation: from rest to maximal exercise, which took place at the Main Meeting of The Physiological Society, Edinburgh, UK on 3 July 2012. It was commissioned by the Editorial Board and reflects the views of the authors.
Contribution of non-endothelium-dependent substances to exercise hyperaemia: are they O2 dependent?
Article first published online: 14 DEC 2012
© 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society
The Journal of Physiology
Volume 590, Issue 24, pages 6307–6320, December 2012
How to Cite
Marshall, J. M. and Ray, C. J. (2012), Contribution of non-endothelium-dependent substances to exercise hyperaemia: are they O2 dependent?. The Journal of Physiology, 590: 6307–6320. doi: 10.1113/jphysiol.2012.240721
- Issue published online: 14 DEC 2012
- Article first published online: 14 DEC 2012
- Accepted manuscript online: 5 OCT 2012 08:09PM EST
- (Received 10 July 2012; accepted after revision 1 October 2012; first published online 1 October 2012)
Abstract This review considers the contributions to exercise hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise hyperaemia by improving O2 supply, limiting the release of O2-dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis.