The functional significance of shear stress-induced vasodilatation in large conduit arteries is unclear since changes in the diameter have little effect on the resistance to blood flow. However, changes in diameter have a relatively large effect on wall shear stress which suggests that the function of flow-mediated dilatation is to reduce wall shear stress. The mean and pulsatile components of shear stress vary widely throughout the arterial system and areas of low mean and high amplitude of wall shear stress are prone to the development of atheroma. In this study, using an in vivo model with the ability to control flow rate and amplitude of flow independently, we investigated the characteristics of the response of the iliac artery to variations in both the mean and amplitude of wall shear stress. The results of this study confirm that increases in mean wall shear stress are an important stimulus for the release of nitric oxide by the endothelium as indicated by changes in arterial diameter and show for the first time, in vivo, that increases in the amplitude of the pulsatile component of shear stress have a small but significant inhibitory effect on this response. A negative feedback mechanism was identified whereby increases in shear stress brought about by increases in blood flow are reduced by the release of nitric oxide from the endothelium causing dilatation of the artery, thus decreasing the stimulus to cell adhesion and, through a direct action of nitric oxide, inhibiting the process of cell adhesion. The results also provide an explanation for the uneven distribution of atheroma throughout the arterial system, which is related to the ratio of pulsatile to mean shear stress and consequent variability in the production of NO.
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