Abstract
Arterial vessels dilate in response to an increase in blood flow. This regulation is based on the ability of endothelial cells to induce relaxation of vascular smooth muscle cells in response to a rise in wall shear stress. Previously, we demonstrated that dimeric glutaraldehyde (dGA) selectively inhibits endothelium-dependent flow-mediated vasodilation via reinforcing endothelial cell stiffness. The present study aims to find out whether the products of oxidative and carbonyl stress, malonyldialdehyde (MDA) and methylglyoxal (MG), are also able to selectively suppress endothelium-dependent flow-mediated dilation. In experiments on anesthetized rats, the changes in vascular conductance of the intact iliac artery, induced by a stepwise flow rise, were studied under control and after infusion of MDA, MG, or DGA into the arterial bed. Simultaneously, a dilation of the artery in response to intra-arterial injection of ACh was tested before and after exposure of the artery to any of the above aldehydes in order to make sure that endothelium retains its ability to relax smooth muscles. Both MDA and DGA strongly and selectively suppressed the flow-mediated dilation of the iliac artery with virtually no effect on the response to ACh. MG suppressed both arterial responses, with a more profound effect exerted on the flow-mediated dilation and a much lesser effect on the response to ACh. These data suggest that aldehydes produced in the process of lipid peroxidation can lead to endothelial dysfunction. Since the endothelial glycocalyx is referred to as a potential mechanosensor that provides the transduction of wall shear stress into the endothelial cell response, the observed detrimental effects of the tested aldehydes on the ability of the iliac artery to tune its diameter in accordance with blood flow can result from the structural derangement of the endothelial glycocalyx.
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