What is the mechanism of flow‐mediated arterial dilatation

Abstract

SUMMARY1. The present review attempts to explain the controversies concerning the mechanism of shear stress-mediated arterial dilatation, commonly called flow-mediated arterial dilatation (FMD). Flow-mediated dilatation occurs in an artery when the blood flow to the organ supplied by the artery is increased.2. There are two hypotheses regarding the stimulus for FMD: (i) a wave of endothelial and smooth muscle hyperpolarization, conducted in a retrograde fashion from the vasodilated peripheral vascular bed towards the relevant conduit artery; and (ii) an increase in shear stress sensed by the endothelial cells.3. The latter hypothesis is associated with two further postulates concerning the method of mechanotransduction of the shear stress stimulus: (i) direct transmission from endothelial cell cytoskeleton to the vascular smooth muscle to induce dilatation; and (ii) indirect transmission to the endothelial cell cytoskeleton via the glycocalyx. The virtues and inconsistencies of these hypotheses are discussed.4. The first hypothesis is excluded because a vasodilated peripheral vascular bed does not cause dilation of the upstream conduit artery if an increase in flow within the conduit artery is prevented and because FMD is completely blocked by inhibition of nitric oxide synthase (NOS).5. It is probable that the stimulus is an increase in shear stress between the blood and the adjacent layer of the arterial wall, the glycocalyx. Ultimately, a change in the endothelial cell cytoskeleton is the likely event that leads to activation of NOS and this activation does not occur without a functioning glycocalyx.

Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow

“…On the other hand, the muscle vascular bed of the leg is larger than that of the skin and plays an important role in vascular function (Markos et al. ). In mice, muscle blood flow of ischemic hind limbs increases after 4‐weeks of daily immersion in carbonated water at 37°C for 10 min (Irie et al.…”

“…This result is supported by the suggestion that enhanced SkBF may be important for improving microvascular vasodilator function (Green et al 2010). On the other hand, the muscle vascular bed of the leg is larger than that of the skin and plays an important role in vascular function (Markos et al 2013). In mice, muscle blood flow of ischemic hind limbs increases after 4-weeks of daily immersion in carbonated water at 37°C for 10 min (Irie et al 2005).…”

Commentary: On the Pathophysiology of Coronary Heart Disease

“…There is another layer between the endothelial cells and the blood within the artery lumen, a layer of gel called the glycocalyx [2], a gel based on glycoproteins. An important function of the glycocalyx-endothelium combination is what is popularly known as "Flow mediated dilatation" [3], but should really be called "Shear stress mediated dilatation". When more blood flow is demanded by the organ supplied by the artery, the increased blood flow causes the artery to widen, by relaxation of the smooth muscle in the arterial wall, in order to accommodate more blood.…”

Flow does not alter eNOS phosphoryation at Ser1179 or Thr495 in preconstricted mouse mesenteric arteries

“…Many arteries in the body dilate in response to increased blood flow, such as during exercise or after acute ischemia (Markos et al. ; Green et al. , ).…”

“…Many arteries in the body dilate in response to increased blood flow, such as during exercise or after acute ischemia (Markos et al 2013;Green et al 2014Green et al , 2017. Increased flow causes shear stress on the endothelial cells that line the artery, and the resulting vasodilation is due at least in part to activation of the endothelium enzyme, eNOS, which generates nitric oxide and causes smooth muscle relaxation (Gilligan et al 1994;Dimmeler et al 1999;Boo and Jo 2003;Sessa 2004;Goto et al 2007;Balligand et al 2009;Green et al 2014;Casey et al 2017).…”