Impairment of endothelium-dependent relaxation of rat aortas by homocysteine thiolactone and attenuation by captopril
Impairment of endothelium-dependent relaxation of rat aortas by homocysteine thiolactone and attenuation by captopril
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DOI：
10.1097/fjc.0b013e31805c9410
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发表时间：
2007-08-01
影响因子：
3
通讯作者：
Liu, Li-Ying
中科院分区：
文献类型：
--
作者：
Liu, Yu-Hui;You, Yu;Liu, Li-Ying
探讨血管紧张素转换酶（ACE）抑制剂对同型半胱氨酸硫代内酯（HTL）诱导的内皮功能障碍的影响。用乙酰胆碱（Ach）和硝普钠（SNP）诱导大鼠胸主动脉环内皮依赖性和非依赖性舒张反应，测定离体主动脉丙二醛（MDA）和一氧化氮（NO）的含量。HTL（3 ~ 30 mM）作用于主动脉环90分钟，可明显抑制Ach诱导的内皮依赖性舒张反应，降低主动脉组织中NO含量，增加MDA含量。用巯甲丙脯酸（0.003 ~ 0.03mM）孵育主动脉环后，可减弱HTL（30 nmol/L）对内皮依赖性舒张（EDR）的抑制作用，显著对抗HTL引起的主动脉组织NO含量的降低和MDA含量的升高。依那普利拉（0.003至0.01 mM）治疗与HTL（30 mM）组在EDR方面无显著差异，但依那普利拉（0.03 mM）和氯沙坦（0.03 mM）可部分恢复HTL（30 mM）引起的EDR。在相同浓度下，卡托普利对HTL抑制乙酰胆碱舒张主动脉的作用强于依那普利拉和氯沙坦。此外，超氧化物歧化酶（SOD，200 U/mL），这是一个清除剂的超氧阴离子，夹竹桃素（0.03 mM），这是一个抑制剂的NADPH氧化酶，和I-精氨酸（3 mmol/L），一氧化氮（NO）的前体，可以减少HTL（30 mM）诱导的抑制EDR。用NO合成酶抑制剂Nomega-nitro-1-arginine methyl ester（L-NAME，0.01 mM）和巯基封闭剂对羟基汞苯甲酸盐（PHMB，0.05 mM）预处理后，可分别取消卡托普利和N-乙酰半胱氨酸的保护作用。上述结果提示HTL诱导的内皮细胞功能障碍可能与NO减少和氧自由基产生有关，而卡托普利可恢复HTL对EDR的抑制作用
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 nunol/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 I-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-1-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