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.
Vasodilator interactions in skeletal muscle blood flow regulation
Article first published online: 22 OCT 2012
© 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society
The Journal of Physiology
Volume 590, Issue 24, pages 6297–6305, December 2012
How to Cite
Hellsten, Y., Nyberg, M., Jensen, L. G. and Mortensen, S. P. (2012), Vasodilator interactions in skeletal muscle blood flow regulation. The Journal of Physiology, 590: 6297–6305. doi: 10.1113/jphysiol.2012.240762
- Issue published online: 14 DEC 2012
- Article first published online: 22 OCT 2012
- Accepted manuscript online: 17 SEP 2012 08:05PM EST
- (Submitted 11 July 2012; accepted after revision 10 September 2012; first published online 17 September 2012)
Abstract During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or on the extraluminal side of the blood vessels. A number of vasodilators have been shown to bring about this increase in blood flow and, importantly, interactions between these compounds seem to be essential for the precise regulation of blood flow. Two compounds stand out as central in these vasodilator interactions: nitric oxide (NO) and prostacyclin. These two vasodilators are both stimulated by several compounds, e.g. adenosine, ATP, acetylcholine and bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperaemic response remains unexplained. It is plausible that this remaining hyperaemia may be explained by cAMP- and cGMP-independent smooth muscle relaxation, such as effects of endothelial derived hyperpolarization factors (EDHFs) or through metabolic modulation of sympathetic effects. The nature and role of EDHF as well as potential novel mechanisms in muscle blood flow regulation remain to be further explored to fully elucidate the regulation of exercise hyperaemia.