Shear Stress, the Endothelium and the Balance between Flow-Induced Contraction and Dilation in Animals and Man

Abstract

Dilation is the most commonly observed diameter change in blood vessels when intraluminal flow increases. However, at very high and low levels of vascular tone the response is constriction. This complex response seems designed to ensure that time-averaged vascular tone levels are restricted to an intermediate range. Flow dilation is initiated predominantly at the surface of the endothelium, probably by conformational change in macromolecules of the extracellular matrix such as glycosaminoglycans. This is associated with changes in ion binding – flow is exquisitely sodium sensitive, and subsequent alteration in cellular function. In the rabbit basilar artery the inward rectifying potassium channel of the endothelium cell is opened by shear stress increase leading to dilation and the voltage-dependent calcium channel of the smooth muscle cells with constriction. In this blood vessel, at any rate, the final response to flow change seems to be predominantly the consequence of the interaction between these two processes.

Estrogen and Tamoxifen Modulate Cerebrovascular Tone in Ovariectomized Female Rats

“…In their natural state, cerebral arteries are exposed continuously to flow and sheer stress, both of which can affect vascular reactivity. 33 Isometric contractile responses may be different had they been investigated in perfused and pressurized vessels under isobaric conditions. In addition, it should also be pointed out that there are currently no suitable models of menopause.…”

Depletion of Intracellular Ca 2+ Stores Sensitizes the Flow-Induced Ca 2+ Influx in Rat Endothelial Cells

“…9 The mechanism by which endothelial cells sense the hemodynamic flow and transform the mechanical signals of flow shear stress into the intracellular Ca 2ϩ signals is still not well understood. Several putative mechanisms have been proposed: (1) shear force may transmit to endothelial cell by interconnecting actin cytoskeleton, thus activating signal transduction cascades without a specific stretch receptor 1 ; (2) flow may cause membrane hyperpolarization, thereby increasing the driving force for extracellular Ca 2ϩ entry 10,11 ; (3) flow may increase ATP concentration in unstirred boundary layer at the cell surface; the elevated ATP may then stimulate Ca 2ϩ influx by opening Ca 2ϩ -permeable purinoceptor P 2 X 4 1,7 ; (4) flow shear stress may displace a layer of glycoproteins in extracellular space, thus modifying ion channels and receptors 12 ; and (5) flow shear stress may activate mechanosensitive nonselective cation channels, resulting in increased Ca 2ϩ influx across the plasmalemma. 8,13 Besides flow shear stress, Ca 2ϩ influx of endothelial cells can be stimulated by Ca 2ϩ -mobilizing agonists such as bradykinin, histamine, and ATP.…”

Increased Plasmin and Serine Proteinase Activity During Flow-Induced Intimal Atrophy in Baboon PTFE Grafts

“…1,2 In rigid prosthetic grafts or stented arteries, which cannot dilate or contract, blood flow alters the size of the lumen by inducing growth or regression of the neointima. 3,4 PTFE grafts used to replace segments of iliac artery in baboons under high-flow conditions (created by placement of a femoral arteriovenous fistula) develop less neointima than those under normal flow.…”