Enalapril improves impairment of SERCA-derived relaxation and enhancement of tyrosine nitration in diabetic rat aorta
Enalapril improves impairment of SERCA-derived relaxation and enhancement of tyrosine nitration in diabetic rat aorta
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DOI：
10.1016/j.ejphar.2006.11.026
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发表时间：
2007-02-05
影响因子：
5
通讯作者：
Kamata, Katsuo
中科院分区：
文献类型：
--
作者：
Taguchi, Kumiko;Kobayashi, Tsuneo;Kamata, Katsuo
我们研究了血管紧张素II和血管平滑肌肌浆网/内质网Ca 2 +-ATP酶（SERCA）功能在已建立的链脲佐菌素诱导的糖尿病中受损的NO诱导的舒张中的参与。血浆血管紧张素II水平，这是在未经治疗的糖尿病大鼠（与年龄匹配的控制）升高，改善与血管紧张素转换酶抑制剂依那普利治疗。慢性依那普利治疗的糖尿病患者的收缩压显著降低（与其他两组相比）。糖尿病大鼠和慢性血管紧张素II输注对照组大鼠的完整动脉，但依那普利治疗的糖尿病大鼠的完整动脉，对乙酰胆碱的内皮依赖性舒张功能受损（与对照组相比）。Angeli盐（一种NO供体）诱导的舒张在糖尿病大鼠（与对照组相比）的内皮剥脱的血管中显著受损，但依那普利治疗使其正常化。在与不可逆的SERCA抑制剂毒胡萝卜素预孵育后，在对照组的内皮剥脱的大鼠中，由Angeli盐诱导的舒张显著受损，但在糖尿病患者中则没有，并且毒胡萝卜素治疗组之间没有显著差异。硝基酪氨酸，过氧亚硝酸盐的间接标志物，显着增加，在主动脉平滑肌糖尿病大鼠，而慢性依那普利给药减少这种增加。这些结果表明，在链脲佐菌素诱导的糖尿病大鼠，过度的血管紧张素II的生产可能会导致过氧亚硝酸盐的产生，这可能会反过来触发血管平滑肌SERCA功能障碍。依那普利可改善糖尿病相关损害。(c)2006 Elsevier B. V.保留所有权利。
We investigated the involvement of angiotensin II and vascular smooth muscle sarco/endoplasmic reticulunt Ca2+-ATPase (SERCA) function in the impaired NO-induced relaxation seen in established streptozotocin-induced diabetes. Plasma angiotensin II levels, which were elevated in untreated diabetic rats (vs age-matched controls), were improved by treatment with the angiotensin-converting enzyme inhibitor enalapril. Systolic blood pressure was significantly decreased in chronic enalaptil-treated diabetics (vs the other two groups). Intact aortae from diabetic rats and chronic angiotensin II-infused control rats, but not those from diabetic rats treated with enalapril, showed impaired endothelium-dependent relaxations to acetylcholine (vs controls). The relaxation induced by Angeli's Salt (a NO donor) was significantly impaired in endotheliumdenuded aortae from diabetic rats (vs controls) but it was normalised by enalapril treatment. After preincubation with the irreversible SERCA inhibitor, thapsigargin, the relaxation induced by Angeli's Salt was significantly impaired in endothelium-denuded aortae from the controls, but not from the diabetics, and there was no significant difference between the thapsigargin-treated groups. Nitrotyrosine, an indirect marker of peroxynitrite, was markedly increased in aortic smooth muscle from diabetic rats, while chronic enalapril administration reduced this increase. These results suggest that in streptozotocin-induced diabetic rats, excessive angiotensin II production may lead to the generation of peroxynittite and that this may in turn trigger a dysfunction of vascular smooth muscle SERCA. Enalapril improved the diabetes-related impairments. (c) 2006 Elsevier B.V.All rights reserved.