Abstract
The strategic location of the endothelium between the flowing intraluminal blood and the vascular smooth muscle cells in the blood vessel wall implies that it should play a crucial role in the blood flow regulation of vascular tone. However, the nature of many of the cellular mechanisms involved in this inter-relationship remain speculative and controversial. The author's hypothesis is that flow can initiate two responses as the result of shear stress activation of a common sensor -the characteristic response is dilation but constriction occurs at lower and can also occur at higher tone levels. At lower levels of tone, flow-contraction and -dilation interact influencing wall tone towards a balance point. Current theories of flow sensing include deformation of viscoelastic molecules attached to the lumenal surface of the endothelium, deformation of the lumenal surface of endothelial cells and flow-dependent, endogenous agonist -lumenal endothelial surface receptor interaction. There are a number of ways in which the endothelium might participate in the coupling of intraluminal flow to smooth muscle tone. That NO is a shear stress-released diffusible dilator factor is well established, although in some vessels, PGI2 seems to play a role of varying importance and additional as yet undefined factors may be involved. There may be mechanical transmission from the deformed endothelial cell via a network involving its cytoskeleton and the subjacent extracellular matrix and perhaps the basement membrane of the smooth muscle cells. The role of electrical coupling if any, is uncertain. The pattern of the response to flow whether constriction or dilation, appears to be related to the level of the membrane potential of the smooth muscle cell. Within the potential range reported to occur in vivo, the dominant response to flow increase is dilation, associated with hyper-polarization. When the smooth muscle cell membrane potential is more negative, flow can cause contraction and depolarization. Under one particular group of experimental conditions in a rabbit cerebral artery, the constrictor and dilator effects were equivalent at a membrane potential of -58 mV. Because it can elicit two opposing responses, flow would be expected to influence vascular tone due to other causes towards this point of balance. In addition when the smooth muscle cells are well depolarized, a contractile element to the flow response can be observed. The significance of this pattern is speculative. It is proposed that flow contraction and dilation acting in unison by modifying tone due to other influences coordinate the responses of the sequential elements of a vascular bed to changes in blood flow to minimize the work required to achieve an effective flow of blood. The efficiency with which this is achieved undoubtedly depends upon the health of the endothelial cells.