Exercise hyperaemia: is anything obligatory but the hyperaemia?

Abstract

Exercise can increase skeletal muscle blood flow by 100-fold over values observed at rest. As this value was 3 to 4 times higher than so-called 'textbook' values at the time it raised a number of issues about cardiovascular control. However, there is a continuing inability to identify the factor or combination of factors that explain this substantial increase in muscle blood flow. Moreover, these governing mechanism(s) must also explain the precise matching of muscle blood flow to metabolic demand and oxygen use or need. The difficulties identifying the mechanisms for exercise hyperaemia are especially disappointing due to the essentially concurrent discovery in the 1980s that the vascular endothelium was a key site of vasomotor control and that nitric oxide (NO) potentially released from nerves, endothelial cells, directly from tissues such as skeletal muscle, or perhaps released from red blood cells, might participate in vascular control in a way that would permit blood flow and metabolism to be closely matched.

Figure 1

Examples of the very high blood flow values observed in exercising (A) human and (B) rat muscles in the 1980s The human data, when expressed per 100 g of active muscle, showed that muscle blood flow values between 200 and 300 ml min⁻¹ (100 g)⁻¹ of tissue were possible. (Figure adapted from Andersen & Saltin, 1985 (A) and Armstrong & Laughlin, 1985 (B), both used with permission.)

Figure 2

Steady state Doppler ultrasound recording of brachial artery blood velocity during rhythmic handgrip exercise Administration of the muscarinic antagonist atropine during forearm exercise did not affect the flow. This demonstrates that ongoing acetylcholine-mediated vasodilatation does not play a major role in exercise hyperaemia. (Figure adapted from Shoemaker et al. 1997, used with permission.)

Figure 3

Effects of external muscle compression on forearm blood flow The rise in flow with rhythmic cuff inflations (○) was small compared with that seen during muscle contractions and only occurred when the limb was in a dependent position (•). These data suggest that the possible contribution of the muscle pump to exercise hyperaemia is modest at best. (Figure from Tschakovsky et al. 1996, used with permission.)

Figure 4

Effects of pharmacological blockade of adenosine receptors, K_ATP channels and NO synthase on the coronary blood flow responses to graded exercise in the dog These data demonstrate the robust nature of the cardiac muscle blood flow responses to exercise and highlight the inability to find a substance or combination of substances that explain this phenomenon. (Figure from Tune et al. 2001, used with permission.)

Figure 5

Blood flow responses to handgripping in patients with cystic fibrosis (CF) in comparison with controls The mutation responsible for CF also limits the ability of the red blood cells to release ATP as oxygen tension falls. These data suggest that ATP release from red blood cells is not a major contributor to exercise hyperaemia. (Figure from Schrage et al. 2005, used with permission.)