Under normal conditions, skeletal muscle is the major component of body mass (30–40% of total). As a consequence, skeletal muscle represents the largest single vascular bed and plays an important role in the maintenance of overall arterial pressure and circulatory homeostasis. In terms of functional behavior, skeletal muscle is unique in the abrupt transition that occurs upon activation of the tissue. Progression from resting conditions to the active state can be accompanied by marked increases in local microvascular blood flow. For example, at rest, total skeletal muscle blood flow is approximately 1000 ml/min (20% of cardiac output), increasing to 15,000 to 25,000 ml/min (85% of cardiac output at V O 2 max https://s3-euw1-ap-pe-df-pch-content-public-u.s3.eu-west-1.amazonaws.com/9780429261312/67f3b946-b8cb-491a-8413-a610fbcb75d5/content/eq11.tif"/> ) in heavy exercise. 1 This ability to alter vascular resistance lies in (1) the microvascular anatomy of skeletal muscle, (2) maintenance of a high level of intrinsic basal tone, and (3) interactions between local and neural regulatory mechanisms.