Regulation of vascular tone: the fat connection.

The study of vascular tone regulation has been based traditionally on layer-specific mechanisms. Three different layers form the blood vessel wall: intima, media, and adventitia. The intima is a monolayer of endothelial cells, which separates circulating blood from the medial layer underneath. The media consists of concentric layers of smooth muscle cells and elastic lamella, varying in number depending on the vessel size. The outer layer of the vessel, the tunica adventitia, is formed of collagen bundles, elastic fibers, fibroblasts, and vasa vasorum. It also harbors perivascular nerve endings. The course of vascular function research has changed through the years. Most early functional studies characterized vasoconstrictor and vasodilator agents and their receptor types and subtypes. At the same time, a bulk of investigation focused on the neural regulation of medial function, characterized perivascular innervation in the adventitia and adventitial-medial border, and described both vasoconstrictor and vasodilator neurotransmitters. The identification in the 1980s of nitric oxide as an endothelium-derived relaxing factor reoriented vascular function studies of the next 2 decades. As a consequence, the endothelial layer is now considered as a paracrine tissue, which produces and releases a variety of contractile and relaxant factors that modulate medial function directly and indirectly through modulation of neurotransmitter release. During this time, the adventitia was regarded as a structural support for the media and its functional role was ignored. However, in recent years there is increasing evidence of a direct modulation of this layer on blood vessel function in a variety of situations.1,2 The development of an easy method to remove the adventitia3 will enable determination of the functional contribution of this layer in the near future and help to define the complex interactions and feedbacks between vascular layers.