New insights into the local regulation of blood flow by perivascular nerves and endothelium.

Blood flow, particularly in the skin, is essential for the success of plastic surgical operations. This review describes recent studies of the perivascular nerves and vascular endothelial cells which regulate blood flow. Perivascular nerves, once considered simply adrenergic or cholinergic, release many types of neurotransmitters, including peptides, purines and nitric oxide. Cotransmission (synthesis, storage and release of more than one transmitter by a single nerve) commonly takes place. Some afferent nerves have an efferent (motor) function and axon reflex control of vascular tone by these "sensory-motor" nerves is more widespread than once thought. Endothelial cells mediate both vasodilatation and vasoconstriction. The endothelial cells can store and release vasoactive substances such as acetylcholine (vasodilator) and endothelin (vasoconstrictor). The origins and functions of such vasoactive substances are discussed. Endothelial vasoactive substances may be of greater significance in the response of blood vessels to local changes while perivascular nerves may be concerned with integration of blood flow in the whole organism. The dual regulation of vascular tone by perivascular nerves and endothelial cells is altered by aging and conditions such as hypertension, as well as by trauma and surgery. Studies of vascular tone in disease and after denervation or mechanical injury suggest possible trophic interactions between perivascular nerves and endothelial cells. Such trophic interactions may be important for growth and development of the two control systems, particularly in the microvasculature where neural-endothelial separation is small.