Exercise hyperaemia: are there any answers yet?

Abstract

This issue of The Journal of Physiology contains five articles that highlight key questions and summarize current thinking about ‘exercise hyperaemia’, an unresolved issue in physiology that remains a real mystery after more than 100 years of research. The articles are based on presentations given at a Journal of Physiology Symposium that was held at the 2007 Experimental Biology meeting in Washington, DC. The central question addressed there was what mechanisms operate to closely match muscle blood flow to metabolism in exercising skeletal (and cardiac) muscle? In the first presentation, Bengt Saltin provided a narrative description of his work in the middle 1980s, which showed that blood flow to contracting muscle could be much higher than previously thought (Saltin, 2007). The efforts of his group to understand the mechanisms for the marked hyperaemia were reviewed and their inability to find a single factor or mechanism responsible for a high fraction of the hyperaemia was discussed. Additionally, the need to vasoconstrict active muscle during heavy whole body exercise to regulate arterial blood pressure was emphasized. In the second presentation, Phillip Clifford provided new ideas about how mechanical interactions between the contracting muscles (i.e. compression) might activate local vasodilator mechanisms in skeletal muscle resistance vessels (Clifford, 2007). New evidence from his group interpreted in the context of older ideas on related topics shows promise for explaining how blood flow can rise so rapidly at the onset of exercise. In the third presentation, Janis Marshall reviewed the many lives that adenosine and related compounds have had as ‘the’ substance or substances that match muscle blood flow and metabolism (Marshall, 2007). A number of examples both supporting and refuting an obligatory role of these substances in exercise hyperaemia were highlighted. It was also emphasized that much of the dilatation caused by these compounds is due to their stimulating NO release from the vascular endothelium but that NO is clearly not obligatory for exercise hyperaemia. While enthusiasm for these compounds has waxed and waned over the past years, how they interact with other dilator systems will be a key factor in evaluating their role in exercise hyperaemia. In the fourth presentation, Dirk Duncker considered how things might be the same or different in cardiac and skeletal muscle (Duncker & Merkus, 2007). His group has shown in several species that the rise in coronary blood flow during exercise is either unaffected or minimally affected by concurrent blockade of multiple vasodilating pathways. This challenges the concept of ‘redundancy’ which suggests that a modest number of key pathways govern exercise hyperaemia and that when one is ‘blocked’ the others compensate in a ‘redundant’ manner and evoke a normal rise in blood flow. In the final presentation, Mike Joyner used data from human models to emphasize that no single factor explains more that a modest fraction of the total rise in flow with exercise (Joyner & Wilkins, 2007). He also highlighted his groups work on the frustrating problem of redundant control with observations that were similar to those noted in the presentations above. Much has been learned about muscle blood flow in the last 20 years and all five of the presenters felt that a number of common themes emerged from the presentations. It is of note that in addition to finding no clear evidence for a dominant vasodilating factor or factors that link muscle metabolism to exercise hyperaemia, these investigators all presented data that raise questions about the idea of redundant control.