Abstract

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.

中文翻译：

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丙二醛和甲基乙二醛诱导的内皮介导的大鼠髂动脉扩张抑制响应血流量升高

摘要

动脉血管扩张以响应血流速率 (BFR) 的增加。这种控制是基于内皮细胞响应壁剪切应力增加而松弛血管平滑肌的能力。以前，我们证明二聚戊二醛 (DGA) 通过增加内皮细胞的硬度选择性地抑制内皮介导的流量依赖性血管舒张。本研究旨在找出氧化和羰基应激的产物丙二醛 (MDA) 和甲基乙二醛 (MG) 是否也可以选择性地抑制内皮介导的流量依赖性扩张。在对麻醉大鼠的实验中，研究了在对照条件下和将 MDA、MG 或 DGA 注入动脉床后，逐步 BFR 升高引起的完整髂动脉水力传导的变化。此外，在暴露于上述任何醛之前和之后，测试了响应于动脉内注射 ACh 的动脉扩张，以确定在这些醛的作用后，内皮是否保留其松弛平滑肌细胞的能力. 我们发现 MDA 和 DGA 都强烈且选择性地抑制了髂动脉的流量依赖性扩张，而对 ACh 的反应几乎没有影响。MG 抑制了两种动脉反应，对血流依赖性扩张产生更深远的影响，对 ACh 反应产生的影响要小得多。这些数据表明脂质过氧化过程中产生的醛类可导致内皮功能障碍。