Todoki K, Okabe E, Kiyose T, Sekishita T, Ito H
Department of Pharmacology, Kanagawa Dental College, Japan.
Am J Physiol. 1992 Mar;262(3 Pt 2):H806-12. doi: 10.1152/ajpheart.1992.262.3.H806.
To understand the direct involvement of free radicals causing reduction in endothelium-dependent relaxation of isolated canine coronary ring preparations, this study was undertaken to examine the effect of free radicals generated from dihydroxy fumarate (DHF) plus Fe(3+)-ADP or from H2O2 plus FeSO4. The vasodilators (acetylcholine, bradykinin, A23187, and nitroglycerin) were given after DHF/Fe(3+)-ADP or H2O2/FeSO4 was removed from the organ chamber. The earlier DHF/Fe(3+)-ADP exposure produced an attenuation of the relaxation of the rings induced by acetylcholine, bradykinin, or A23187 but not of the relaxation induced by nitroglycerin. The observed effect of previous DHF/Fe(3+)-ADP exposure was significantly protected in the vessels isolated from the dogs treated with alpha-tocopherol. In the experiments for assessing the effect of various scavengers, 1O2 scavenger histidine or iron chelator deferoxamine effectively protected the attenuation induced by DHF/Fe(3+)-ADP exposure of the relaxation elicited by acetylcholine; superoxide dismutase (SOD), catalase, or dimethyl sulfoxide (DMSO) had no effect on this system. Furthermore, the relaxation elicited by acetylcholine, but not nitroglycerin, was significantly attenuated by the earlier exposure to .OH generated by Fenton's reagent (H2O2+FeSO4); the attenuation was significantly protected by DMSO. These results are consistent with the view that .OH, 1O2, and/or iron-dependent reactive species selectively damage endothelium-dependent relaxation as opposed to endothelium-independent relaxation in endothelium-intact coronary ring preparations. It is also postulated that lipid peroxidation may be responsible for this effect.
为了解自由基直接参与导致离体犬冠状动脉环制剂内皮依赖性舒张功能降低的情况，本研究旨在检测由二羟基富马酸（DHF）加Fe(3+)-ADP或由过氧化氢（H2O2）加硫酸亚铁（FeSO4）产生的自由基的作用。在将DHF/Fe(3+)-ADP或H2O2/FeSO4从器官浴槽中去除后，给予血管舒张剂（乙酰胆碱、缓激肽、A23187和硝酸甘油）。早期暴露于DHF/Fe(3+)-ADP会减弱由乙酰胆碱、缓激肽或A23187诱导的血管环舒张，但不会减弱由硝酸甘油诱导的舒张。在从用α-生育酚处理的犬分离的血管中，先前DHF/Fe(3+)-ADP暴露所观察到的效应得到了显著保护。在评估各种清除剂作用的实验中，单线态氧清除剂组氨酸或铁螯合剂去铁胺有效保护了由DHF/Fe(3+)-ADP暴露引起的乙酰胆碱诱导的舒张减弱；超氧化物歧化酶（SOD）、过氧化氢酶或二甲基亚砜（DMSO）对该系统无影响。此外，早期暴露于由芬顿试剂（H2O2+FeSO4）产生的羟基自由基（·OH）会显著减弱由乙酰胆碱而非硝酸甘油诱导的舒张；DMSO可显著保护这种减弱。这些结果与以下观点一致，即羟基自由基（·OH）、单线态氧（1O2）和/或铁依赖性反应性物种选择性地损害内皮完整的冠状动脉环制剂中的内皮依赖性舒张，而非内皮非依赖性舒张。还推测脂质过氧化可能是造成这种效应的原因。
