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Acta Physiol Scand. 2000 Apr;168(4):531-41.

Coupling of muscle metabolism and muscle blood flow in capillary units during contraction.

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  • 1Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.


Muscle blood flow is tightly coupled to the level of skeletal muscle activity: Indices of skeletal muscle metabolic rate, for example oxygen consumption or muscle work, are directly related to the magnitude of the change in muscle blood flow. Despite the large amount that is known about individual aspects of local metabolic vasodilation, the mechanisms underlying integrated aspects of the response remain largely unknown. Arteriolar dilation serves both to increase blood flow through the muscle and also to recruit capillaries and control capillary blood flow distribution. Conceptually, these two apparently separate functions of larger vs. more terminal arterioles (where larger vessels subserve conductance changes while the smaller more distal vessels have a primary role in capillary blood flow control) can be met, at least in part, by differential sensitivity of large vs. small arterioles to metabolites and agonists relevant to the metabolic response. However, longitudinal differences in sensitivity through the arteriolar network will not by themselves account for observed heterogeneities in capillary perfusion or for the close matching between blood flow and metabolism that occurs even in mixed muscles. In mixed skeletal muscles, fibres of widely different metabolic profile are dispersed throughout the muscle and even fibres of a single motor unit are not perfused by common arterioles but are matched with arterioles arising from widely disparate regions within the microvascular network. In this review we present findings that support the notion that capillaries are an integral part of the mechanism underlying this close matching between blood flow and metabolism. We review studies that indicate that capillaries are capable of responding to stimuli in their immediate environment and, importantly, are able to communicate with arterioles located remotely upstream in the arteriolar tree. Not only can skeletal muscle capillary endothelial cells induce remote arteriolar vasodilatory and vasoconstrictor responses to pharmacological stimuli such as acetylcholine or noradrenaline, but they can also initiate these remote arteriolar responses in response to skeletal muscle contraction. Capillary endothelial cells respond to skeletal muscle contraction by transmitting a dilatory signal to at least three branch orders of arterioles proximal to the capillary; these upstream dilations present a mechanism whereby capillaries can initiate their own recruitment, and whereby increased blood flow can be directed only to those exchange vessels associated with the contracting muscle fibres and where, presumably, the initiating signal is sensed. This signal involves KATP channels, although their location (on endothelial, vascular smooth muscle or skeletal muscle cells) is not yet known and has a nitric oxide-dependent component. The studies reviewed here thus indicate that capillaries have the capacity to play an active role in co-ordination of muscle blood flow responses to changed muscle metabolism. Much more remains to be learned, however, about the mechanisms underlying the signals generated by the contracting muscle and the mechanisms of transmission of the signals upstream.

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