Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vasoactive substances. Muscle blood flow is increased within the first second after a single contraction and stabilizes within approximately 30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise to the sustained elevation during steady-state exercise. Exercise hyperemia is therefore thought to be the result of an integrated response of more than one vasodilator mechanism. To date, the identity of vasoactive substances involved in the regulation of exercise hyperemia remains uncertain. Numerous vasodilators such as adenosine, ATP, potassium, hypoxia, hydrogen ion, nitric oxide, prostanoids, and endothelium-derived hyperpolarizing factor have been proposed to be of importance; however, there is little support for any single vasodilator being essential for exercise hyperemia. Because elevated blood flow cannot be explained by the failure of any single vasodilator, a consensus is beginning to emerge for redundancy among vasodilators, where one vasoactive compound may take over when the formation of another is compromised. Conducted vasodilation or flow-mediated vasodilation may explain dilation in vessels (i.e., feed arteries) not directly exposed to vasodilator substances in the interstitium. Future investigations should focus on identifying novel vasodilators and the interaction between vasodilators by simultaneous inhibition of multiple vasodilator pathways.

No abstract

To date, no satisfactory explanation has been provided for the immediate increase in blood flow to skeletal muscles at the onset of exercise. We hypothesized that rapid vasodilatation is a consequence of release of a vasoactive substance from the endothelium owing to mechanical deformation of the vasculature during contraction. Rat soleus feed arteries were isolated, removed and mounted on micropipettes in a sealed chamber. Arteries were pressurized to 68 mmHg, and luminal diameter was measured using an inverted microscope. Pressure pulses of 600 mmHg were delivered for 1 s, 5 s, and as a series of five repeated 1 s pulses with 1 s between pulses. During application of external pressure the lumen of the artery was completely closed, but immediately following release of pressure the diameter was significantly increased. In intact arteries (series 1, n = 6) for the 1 s pulse, 5 s pulse and series of five 1 s pulses, the peak increases in diameter were, respectively, (mean ± S.E.M.) 16 ± 2, 14 ± 2 and 27 ± 3%, with respective times from release of pressure to peak diameter of 4.1 ± 0.3, 4.6 ± 0.7 and 2.8 ± 0.4 s. In series 2 (n = 9) the arteries increased diameter by 15 ± 2, 15 ± 2 and 30 ± 3% before and by 8 ± 1, 8 ± 1 and 21 ± 2% after removal of the endothelium with air. The important new finding in these experiments is that mechanical compression caused dilatation of skeletal muscle feed arteries with a time course similar to the change in blood flow after a brief muscle contraction. The magnitude of dilatation was not affected by increasing the duration of compression but was enhanced by increasing the number of compressions. Since removal of the endothelium reduced but did not abolish the dilatation in response to mechanical compression, it appears that the dilatation is mediated by both endothelium-dependent and -independent signalling pathways.

Is there sympathetic vasoconstriction in exercising skeletal muscle? Although convincing evidence exists that demonstrates vasoconstriction in active muscle, the proposition that the sympathetic nervous system constricts skeletal muscle during exercise poses a paradox, given the robust vasodilation that occurs in muscle during exercise. Ultimately, muscle perfusion is a balance between metabolic vasodilation and sympathetic vasoconstriction.

The mechanism for exercise hyperaemia is a century old enigma. Much of the research on the topic has focused on the factors controlling skeletal muscle blood flow during steady-state dynamic exercise. It is likely that the factors which initiate the increase in blood flow are distinct from those which sustain the elevated blood flow. There is now convincing evidence that there is rapid vasodilatation following release of muscle contraction. Metabolic, neural and acetylcholine spillover mechanisms do not appear to explain the initial dilatation. Heretofore there has been only circumstantial evidence regarding the role of potassium released by skeletal muscle fibres. Studies which interrupt potassium-mediated dilatation are just emerging and are not conclusive. In addition, the latency of the vascular smooth muscle response to potassium makes it desirable to identify a mechanism that does not rely on diffusion of a vasoactive agent. Compression of the intramuscular arterioles during contraction could activate a mechanosensitive response by the vascular smooth muscle and/or endothelium. Recent in vitro and in vivo data support the notion that brief periods of mechanical compression elicit rapid vasodilatation. Thus, vascular compression could represent a feedforward mechanism for initiating skeletal muscle vasodilatation at the onset of exercise.