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.

T he aim of the study was to determine the effect of insulin on a conduit artery. In a closed-off test segment of iliac artery in vivo in anaethetised pigs, pressure was kept constant. During the first 10 minutes of exposure to hyperinsulinaemic blood, the test segment diameter was 3.63±0.64 mm (mean ± SD). Dilatation occurred after 10 minutes when the test segment diameter increased to 3.80±0.62 mm (mean ± SD), p=0.0006, n=10. The increase in diameter with the vehicle for insulin in blood was -0.0775±0.116 mm (mean ± SD, n=6) and with hyperinsulin in blood was 0.165±0.124 mm (mean ± SD, n=10), p=0.0024. Dilatation with hyperinsulin was 0.229±0.116 mm (mean ± SD) versus insulin plus 250 µg/ml of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), 0.041±0.026 mm (mean ± SD), p=0.0313, n=6. No evidence of arterial constriction was observed in the presence of L-NAME. We conclude that insulin has a direct relaxing effect on the smooth muscle in the wall of conduit artery, mediated by nitric oxide. Br J Diabetes Vasc Dis 2011;11:130-136.