Ramipril prevents endothelial dysfunction induced by oxidized low-density lipoproteins: a bradykinin-dependent mechanism.
Ramipril prevents endothelial dysfunction induced by oxidized low-density lipoproteins: a bradykinin-dependent mechanism.
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雷米普利可预防氧化低密度脂蛋白引起的内皮功能障碍：一种缓激肽依赖性机制。
作者：
G. Berkenboom;I. Langer;Y. Carpentier;K. Grosfils;J. Fontaine
我们希望确定是否急性毒性作用的氧化低密度脂蛋白的衰减，从大鼠分离血管紧张素转换酶（ACE）抑制剂长期治疗。在与人氧化LDL（300 μ g/mL）孵育的主动脉环中，对乙酰胆碱的内皮依赖性舒张减弱，但对A23187和硝普钠的内皮依赖性舒张不减弱。氧化LDL的这种毒性作用在与氧化LDL和一氧化氮（NO）前体L-精氨酸（0.3 mmol/L）共孵育的制剂中被完全阻止。在从大鼠经口给予10 mg/kg雷米普利（第1组）或1 mg/kg雷米普利（第2组）6周后分离的动脉瘤中，氧化LDL的这种毒性作用也明显减弱。与此相反，在从与雷米普利共处理的大鼠中分离的大鼠中，（10 mg/kg），持续6周，并皮下注射Hoe 140（一种B2激肽拮抗剂），500 μ g/kg/天，持续最后2周（组3），或来自用氯沙坦口服治疗6周的大鼠（AT 1型血管紧张素II受体拮抗剂），20 mg/kg（第4组），氧化低密度脂蛋白对乙酰胆碱诱导的舒张作用的抑制作用与对照组（第5组）中观察到的相似。此外，长期治疗与雷米普利增加松弛乙酰胆碱在第1组和第2组，也松弛A23187和主动脉cGMP含量在第1组，这表明一个增强的NO的可用性。因此，长期ACE抑制对氧化LDL的急性血管毒性的保护作用是缓激肽依赖性的，似乎涉及通过内皮B2激肽受体促进NO释放。
We wished to determine whether the acute toxic effects of oxidized LDL are attenuated in aortas isolated from rats chronically treated with an angiotensin-converting enzyme (ACE) inhibitor. In aortic rings incubated with human oxidized LDL (300 microg/mL), the endothelium-dependent relaxations to acetylcholine were attenuated, but not those to A23187 and to nitroprusside. This toxic effect of oxidized LDL was completely prevented in preparations coincubated with oxidized LDL and the nitric oxide (NO) precursor L-arginine (0.3 mmol/L). In aortas isolated from rats orally treated for 6 weeks with 10 mg/kg ramipril (group 1) or 1 mg/kg ramipril (group 2), this toxic effect of oxidized LDL was also markedly attenuated. In contrast, in aortas isolated from rats cotreated with ramipril (10 mg/kg) for 6 weeks and subcutaneous injections of Hoe 140 (a B2 kinin antagonist), 500 microg/kg per day for the last 2 weeks (group 3) or from rats orally treated for 6 weeks with losartan (an AT1-type angiotensin II receptor antagonist), 20 mg/kg (group 4), the inhibitory effect of oxidized LDL on acetylcholine-induced relaxations was similar to that observed in the control group (group 5). Moreover, long-term treatment with ramipril increased relaxations to acetylcholine in groups 1 and 2 and also relaxations to A23187 and aortic cGMP content in group 1, suggesting an enhanced NO availability. Thus, the protective effect of long-term ACE inhibition against the acute vascular toxicity of oxidized LDL is bradykinin dependent and seems to involve a facilitation of NO release via endothelial B2 kinin receptors.
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氧化低密度脂蛋白引起猪冠状动脉收缩并抑制内皮依赖性舒张。
DOI：
10.1172/jci114718
发表时间：
1990
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Simon,BC;Cunningham,LD;Cohen,RA
通讯作者：
Cohen,RA
DOI：
10.1073/pnas.84.9.2995
发表时间：
1987-05-01
影响因子：
11.1
作者：
QUINN, MT;PARTHASARATHY, S;STEINBERG, D
通讯作者：
STEINBERG, D
影响因子：
20.1
作者：
NIU, XF;SMITH, CW;KUBES, P
通讯作者：
KUBES, P
DOI：
10.1002/jss.400130107
发表时间：
1980-01-01
期刊：
JOURNAL OF SUPRAMOLECULAR STRUCTURE
影响因子：
--
作者：
BROWN, MS;BASU, SK;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
DOI：
10.1073/pnas.81.12.3883
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
STEINBRECHER, UP;PARTHASARATHY, S;STEINBERG, D
通讯作者：
STEINBERG, D