To explore the effects of angiotensin-converting enzyme (ACE) inhibitors on endothelial dysfunction induced by homocysteine thiolactone (HTL). Both endothelium-dependent relaxation and nondependent relaxation of thoracic aortic rings in rats induced by acetylcholine (Ach) or sodium nitroprusside (SNP) and biochemical parameters including malondialdehyde (MDA) and nitric oxide (NO) were measured in rat isolated aorta. Exposure of aortic rings to HTL (3 to 30 mM) for 90 minutes made a significant inhibition of endothelium-dependent relaxation induced by Ach, decreased contents of NO, and increased MDA concentration in aortic tissue. After incubation of aortic rings with captopril (0.003 to 0.03 mM) attenuated the inhibition of endothelium-dependent relaxation (EDR) and significantly resisted the decrease of NO content and elevation of MDA concentration caused by HTL (30 mmol/L) in aortic tissues, a similarly protective effect was observed when the aortic rings were incubated with both N-acetylcysteine (0.05 mM). Treatment with enalaprilat (0.003 to 0.01 mM) made no significant difference with the HTL (30 mM) group regarding EDR, but enalaprilat (0.03 mM) and losartan (0.03 mM) could partly restore the EDR in response to HTL (30 mM). Captopril was more effective than enalaprilat and losartan in attenuation of the inhibition of on acetylcholine-stimulated aortic relaxation by HTL in the same concentration. Moreover, superoxide dismutase (SOD, 200 U/mL), which is a scavenger of superoxide anions, apocynin (0.03 mM), which is an inhibitor of NADPH oxidase, and l-Arginine (3 mmol/L), a precursor of nitric oxide (NO), could reduce HTL (30 mM)-induced inhibition of EDR. After pretreatment with not only the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME, 0.01 mM) but also the free sulfhydryl group blocking agent p-hydroxymercurybenzoate (PHMB, 0.05 mM) could abolish the protection of captopril and N-acetylcysteine, respectively. These results suggest that mechanisms of endothelial dysfunction induced by HTL may include the decrease of NO and the generation of oxygen free radicals and that captopril can restore the inhibition of EDR induced by HTL in isolated rat aorta, which may be related to scavenging oxygen free radicals and may be sulfhydryl-dependent.
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【Impairment of endothelium-dependent relaxation of rat aortas by homocysteine thiolactone and attenuation by captopril.].
【高半胱氨酸硫代内酯对大鼠主动脉内皮依赖性松弛的损害和卡托普利的减弱。】
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DOI：10.1097/FJC.0b013e31805c9410文章类型：杂志文章
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：探讨血管紧张素转换酶（ACE）抑制剂对高半胱氨酸硫代内酯（HTL）诱导的内皮功能障碍的影响。在大鼠离体主动脉中，测量了乙酰胆碱（Ach）或硝普钠（SNP）诱导的大鼠胸主动脉环的内皮依赖性舒张和非依赖性舒张以及包括丙二醛（MDA）和一氧化氮（NO）在内的生化参数。将主动脉环暴露于HTL（3至30 mM）90分钟可显着抑制Ach诱导的内皮依赖性舒张，减少NO含量并增加主动脉组织中的MDA浓度。用卡托普利（0.003至0.03 mM）孵育主动脉环后，减弱了对血管内皮依赖性舒张（EDR）的抑制作用，并显着抑制了HTL（30 mmol / L）引起的NO含量降低和MDA浓度升高，当主动脉环与两个N-乙酰半胱氨酸（0.05 mM）一起孵育时，观察到类似的保护作用。依那普利拉（0.003至0.01 mM）的治疗与HTL（30 mM）组在EDR方面无显着差异，但依那普利拉（0.03 mM）和氯沙坦（0.03 mM）可以部分响应HTL（30 mM）恢复EDR。在相同浓度下，卡托普利比依那普利拉和氯沙坦更有效地抑制HTL对乙酰胆碱刺激的主动脉舒张的抑制作用。此外，作为超氧化物阴离子的清除剂的超氧化物歧化酶（SOD，200 U / mL），作为NADPH氧化酶抑制剂的载脂蛋白（0.03 mM）和作为硝酸前体的l-精氨酸（3 mmol / L）。一氧化氮（NO）可以降低HTL（30 mM）对EDR的抑制作用。用NO合酶抑制剂Nomega-硝基-1-精氨酸甲酯（L-NAME，0.01 mM）预处理后，游离巯基封闭剂对羟基汞基苯甲酸酯（PHMB，0.05 mM）都可以取消卡托普利和N-乙酰半胱氨酸分别。这些结果表明，HTL诱导的内皮功能障碍的机制可能包括NO的减少和氧自由基的产生，并且卡托普利可以恢复HTL诱导的离体大鼠主动脉对EDR的抑制作用，这可能与清除氧自由基有关。并且可能是巯基依赖性的。
