Local control of blood flow during active hyperaemia: what kinds of integration are important?

The focus of this review is on local mechanisms modifying arteriolar resistance to match blood flow to metabolism. In skeletal muscle many local mediators are known, including K(+) , nitric oxide (NO), purines and prostaglandins. Each accounts for about 30% of the response; it is widely held that these act redundantly: this concept awaits systematic testing. Understanding signal integration also requires consideration of microvascular network morphology in relation to local communication pathways between endothelial and smooth muscle cells (which are critical for many local responses, including dilatation to skeletal muscle contraction) and in relation to the spread of vasodilator signals up- and downstream throughout the network. Mechanisms mediating the spread of dilatation from local to remote sites have been well studied using acetylcholine (ACh), but remote dilatations to contraction of skeletal muscle fibres also occur. Importantly, these mechanisms clearly differ from those initiated by ACh, but much remains undefined. Furthermore, capillaries contribute to metabolic dilatation as they dilate arterioles directly upstream in response to vasoactive agents or contraction of adjacent muscle fibres. Given the dispersed arrangement of motor units, precise matching of flow to metabolism is not attainable unless signals are initiated only by 'active' capillaries. As motor units are recruited, signals that direct blood flow towards these active fibres will eventually be supported by local and spreading responses in the arterioles associated with those fibres. Thus, mechanisms of integration of vasodilator signalling across elements of the microvasculature remain an important area of focus for new studies.