CELL-TO-CELL COMMUNICATION COORDINATES BLOOD-FLOW CONTROL

The control of tissue blood flow is a dynamic process exemplified by the interaction among physical, chemical, and electrical events occurring within the vessel wall and between the vasculature and tissue parenchyma. The range of blood flow control achieved in vivo is illustrated by functional hyperemia in exercising skeletal muscle: maximal flow can exceed resting values by more than 50-fold. Blood flow control is integrated among many vessel segments, beginning with resistance arteries external to the muscle and encompassing the arteriolar network within the muscle. As metabolic demand increases, the locus of blood flow control shifts from distal arterioles, which control capillary perfusion and blood flow distribution within the tissue, to the proximal arterioles and resistance arteries, which control the total volume of flow into the muscle. A fundamental question centers on how this vasomotor activity is actually coordinated throughout the resistance network. The interaction within and among vascular segments can be explained by chemical and electrical signals to smooth muscle cells (SMCs) and endothelial cells (ECs) in response to changes in transmural pressure as well as luminal shear stress. Increasing pressure results in SMC contraction via the myogenic response. Increasing flow stimulates ECs to release autacoids (eg, nitric oxide), which relax SMCs. Pressure and flow thereby provide opposing mechanical stimuli that interact in the maintenance of vasomotor tone throughout the resistance network. Vasomotor signals are also conducted along arterioles through cell-to-cell coupling between ECs and SMCs, thereby coordinating vasomotor activity of cells within a branch and among branches. Adrenergic innervation influences each of these relations, as do the metabolic and mechanical effects of muscle contraction. The contribution of respective mechanisms to the control of blood flow varies with location in the resistance network, yet the interaction between mechanisms results in tissue perfusion in accord with the local requirements of parenchymal cells.