Malonyldialdehyde- and Methylglyoxal-Induced Suppression of Endothelium-Mediated Dilation of Rat Iliac Artery in Response to Elevation of Blood Flow

• Published in: Journal of evolutionary biochemistry and physiology 2021-07, Vol.57 (4), p.792-802
• Main Authors: Ermishkin, V. V., Lukoshkova, E. V., Melkumyants, A. M.
• Format: Article
• Language: English
• Subjects: Aldehydes; Animal Physiology; Biochemistry; Biomedical and Life Sciences; Blood flow; Carbonyl compounds; Endothelial cells; Endothelium; Evolutionary Biology; Experimental Papers; Life Sciences; Lipid peroxidation; Pyruvaldehyde; Shear stress; Smooth muscle; Vasodilation; Veins & arteries
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093021040050

Arterial vessels dilate in response to an increase in blood flow rate (BFR). This control is based on ability of endotheliocytes to relax vascular smooth muscles in response to an increase in the wall shear stress. Previously, we demonstrated that dimeric glutaraldehyde (DGA) selectively inhibited the endothelium-mediated flow-dependent vasodilation via increasing the stiffness of endotheliocytes. The present study aims to find out whether the products of oxidative and carbonyl stress, malonyldialdehyde (MDA) and methylglyoxal (MG), can also selectively suppress the endothelium-mediated flow-dependent dilation. In experiments on anesthetized rats, the changes in hydraulic conductance of the intact iliac artery induced by a stepwise BFR elevation were studied under the control conditions and after infusion of MDA, MG, or DGA into the arterial bed. In addition, a dilation of the artery in response to intra-arterial injection of ACh was tested before and after its exposure to any of the above aldehydes to determine whether the endothelium retained its ability to relax the smooth muscle cells after the action of these aldehydes. We found that both MDA and DGA strongly and selectively suppresses the flow-dependent dilation of 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-dependent dilation and a much lesser one 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 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 iliac artery to tune its diameter in accordance to BFR can result from the structural derangement of the endothelial glycocalyx.