Capillary communication: the role of capillaries in sensing the tissue environment, coordinating the microvascular, and controlling blood flow.

Historically, capillaries have been viewed as the microvascular site for flux of nutrients to cells and removal of waste products. Capillaries are the most numerous blood vessel segment within the tissue, whose vascular wall consists of only a single layer of endothelial cells and are situated within microns of each cell of the tissue, all of which optimizes capillaries for the exchange of nutrients between the blood compartment and the interstitial space of tissues. There is, however, a growing body of evidence to support that capillaries play an important role in sensing the tissue environment, coordinating microvascular network responses, and controlling blood flow. Much of our growing understanding of capillaries stems from work in skeletal muscle and more recent work in the brain, where capillaries can be stimulated by products released from cells of the tissue during increased activity and are able to communicate with upstream and downstream vascular segments, enabling capillaries to sense the activity levels of the tissue and send signals to the microvascular network to coordinate the blood flow response. This review will focus on the emerging role that capillaries play in communication between cells of the tissue and the vascular network required to direct blood flow to active cells in skeletal muscle and the brain. We will also highlight the emerging central role that disruptions in capillary communication may play in blood flow dysregulation, pathophysiology, and disease.