Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction
Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction
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DOI：
10.1152/ajpheart.00372.2006
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Diz, Debra I.
中科院分区：
文献类型：
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作者：
Benter, Ibrahim F.;Yousif, Mariam H. M.;Diz, Debra I.
这项研究的目的是验证血管紧张素-(1-7)[Ang(1-7)]或Ang-(1-7)非肽类似物AVE-0991可以对糖尿病引起的心血管功能障碍产生保护作用的假设。用Ang-(1-7)(576µg·kg~(-1)·kg~(-1))慢性给药(4wk)。Ave-0991(-1天ip)或AVE-0991(576微克·kg(-1)天(.1天ip))对蛋白尿、离体颈动脉、肾动脉环段和肠系膜床血管对血管活性激动剂的反应性，以及对糖尿病大鼠缺血再灌流后心脏的恢复。在诱导糖尿病和/或应用Ang-(1-7)或AVE-0991治疗后4wk处死动物。糖尿病组尿蛋白(231+/-2 mg/24 h)显著高于对照组(88+/-6 mg/24 h)。Ang-(1-7)或AVE-0991可显著降低糖尿病大鼠的尿蛋白(分别为183+/-16和149+/-15 mg/24 h)。使用Ang-(1-7)或AVE-0991治疗也可以防止糖尿病引起的血管对去甲肾上腺素、内皮素-1、血管紧张素II、卡巴胆碱和组胺的异常反应。在离体灌流心中，Ang-(1-7)或AVE-0991处理的动物从40分钟的全脑缺血中恢复左心功能明显更好。这些结果表明，激活Ang-(17)介导的信号转导可能是减少糖尿病患者心血管事件的重要治疗策略。
The aim of this study was to test the hypothesis that treatment with angiotensin-(1-7) [ANG(1-7)] or ANG-(1-7) nonpeptide analog AVE-0991 can produce protection against diabetes-induced cardiovascular dysfunction. We examined the influence of chronic treatment (4 wk) with ANG-(1-7) (576 mu g(.)kg(-1) (.) day(-1) ip) or AVE- 0991 (576 mu g(.)kg(-1.)day(.1) ip) on proteinuria, vascular responsiveness of isolated carotid and renal artery ring segments and mesenteric bed to vasoactive agonists, and cardiac recovery from ischemia-reperfusion in streptozotocin-treated rats (diabetes). Animals were killed 4 wk after induction of diabetes and/or treatment with ANG-(1-7) or AVE-0991. There was a significant increase in urine protein (231 +/- 2 mg/24 h) in diabetic animals compared with controls (88 +/- 6 mg/24 h). Treatment of diabetic animals with ANG-(1-7) or AVE- 0991 resulted in a significant reduction in urine protein compared with vehicle-treated diabetic animals (183 +/- 16 and 149 +/- 15 mg/ 24 h, respectively). Treatment with ANG-(1-7) or AVE-0991 also prevented the diabetes-induced abnormal vascular responsiveness to norepinephrine, endothelin-1, angiotensin II, carbachol, and histamine in the perfused mesenteric bed and isolated carotid and renal arteries. In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischemia was significantly better in ANG-(1-7)- or AVE- 0991-treated animals. These results suggest that activation of ANG-(17)- mediated signal transduction could be an important therapeutic strategy to reduce cardiovascular events in diabetic patients.