Figure 3. Increases in wall shear stress induced by elevated blood flow induce endothelium-dependent vasodilation (shear stress-induced or flow-mediated dilation) by a mechanism that is independent of changes in vascular pressure and conducted vasodilator responses.

Figure 3

Increases in wall shear stress induced by elevated blood flow induce endothelium-dependent vasodilation (shear stress-induced or flow-mediated dilation) by a mechanism that is independent of changes in vascular pressure and conducted vasodilator responses. Upper panel: Epoxyeicosatrienoic acids (EETS) are synthesized from arachidonic acid via the enzymatic activity of cytochrome P450 epoxygenases 2C and 2J (CYP450) after agonist binding or induction of a shear stress (usually associated with increased blood flow) in endothelial cells. The EETs are transferrable factors that diffuse to underlying vascular smooth muscle cells to elicit vasodilation in some arteries by activating large conductance, calcium-activated potassium channels (BKCa) by a guanine nucleotide binding protein-dependent mechanism (left endothelial cell in upper panel). The ensuing potassium efflux results in membrane hyperpolarization and relaxation of vascular smooth muscle. In other arteries, EETs act in a paracrine manner by stimulating endothelial small (SKCa) and intermediate (IKCa) conductance, calcium-activated potassium channels (right endothelial cell in upper panel). Subsequent potassium ion efflux into the subendothelial space, which in turn activates the sodium/potassium ATPase (Na/K ATPase) or inward rectifying potassium channels (Kir) on vascular smooth muscle cells. Potassium efflux hyperpolarizes the smooth muscle membrane, inhibits the influx of calcium ions, thereby producing vasorelaxation. Endothelial hyperpolarization is also transmitted to vascular smooth muscle via myoendothelial gap junctions (MEJ). Lower panel: Although the mechanosensors involved in detecting the changes in wall shear stress are unclear, there is evidence suggesting that tyrosine kinase receptors, certain G protein coupled receptors, caveolae, focal adhesion proteins, tensegrity (the endothelial cell cytoskeleton), glycocalyx, interendothelial junctional protein complexes, and primary cilia on endothelial cells may play important roles as mechanotransduction elements that elicit relaxation of the underlying vascular smooth muscle cells by release of a diffusible factor such as nitric oxide (NO), prostaglandins (PGs), EETs and hydrogen peroxide (H2O2]. It is important to note that the transferrable factors produced and involved in a given flow-mediated dilation depend on the nature of the agonist, shear stress stimulus, and endothelial phenotype. In both panels, the internal elastic lamina (basement membrane) between the endothelium and vascular smooth muscle is omitted for clarity.

From: Chapter 3, Regulation of Vascular Tone in Skeletal Muscle

Cover of Skeletal Muscle Circulation
Skeletal Muscle Circulation.
Korthuis RJ.
San Rafael (CA): Morgan & Claypool Life Sciences; 2011.
Copyright © 2011 by Morgan & Claypool Life Sciences.

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