Effects of a selective bradykinin B1 receptor antagonist on increased plasma extravasation in streptozotocin-induced diabetic rats:: Distinct vasculopathic profile of major key organs
Effects of a selective bradykinin B1 receptor antagonist on increased plasma extravasation in streptozotocin-induced diabetic rats:: Distinct vasculopathic profile of major key organs
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DOI：
10.1016/j.ejphar.2005.03.023
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发表时间：
2005-05-02
影响因子：
5
通讯作者：
Sirois, P
中科院分区：
文献类型：
--
作者：
Lawson, SR;Gabra, BH;Sirois, P
弥漫性血管病变是与胰岛素依赖型1型糖尿病相关的发病率和死亡率增加的共同特征。内皮功能障碍后，血管通透性增加导致周围组织发生血浆外渗。这种微血管和大血管并发症随着时间的推移而发展，并导致水肿、高血压、心肌病、肾衰竭（肾病）和其他并发症（神经病、视网膜病）。在本研究中，我们研究了选择性缓激肽B受体拮抗剂R-954对链脲佐菌素（STZ）诱导的糖尿病Wistar大鼠血管通透性增加的影响。在STZ给药后1周和4周，在选定的靶组织（左和右心房、心室、肺、腹部和胸部动脉瘤、肝、脾、肾皮质和髓质）中使用伊文思蓝染料测定血浆外渗。在STZ 1周大鼠的腹主动脉、皮质、髓质和脾脏中血管通透性显著增加，并在糖尿病4周时保持升高。两个心房显示血管通透性增加后4周STZ管理。R-954（2 mg/kg，推注，皮下注射），在给予伊文思蓝染料之前2小时给予1周和4周的糖尿病大鼠显著抑制（48- 100%）受糖尿病影响的大多数测试组织中的血浆渗漏，而对健康大鼠没有影响。这些结果表明，诱导型缓激肽B 1受体亚型参与了糖尿病大鼠血管通透性的调节，并提示选择性缓激肽B 1受体拮抗剂可能在减少糖尿病血管并发症中具有有益的作用。(c)2005 Elsevier B. V.保留所有权利。
Diffuse vasculopathy is a common feature of the morbidity and increased mortality associated with insulino-dependent type 1 diabetes. Increased vascular permeability leading to plasma extravasation occurs in surrounding tissues following endothelial dysfunction. Such micro-and macro-vascular complications develop over time and lead to oedema, hypertension, cardiomyopathy, renal failure (nephropathy) and other complications (neuropathy, retinopathy). In the present investigation, we studied the effect of a selective bradykinin B, receptor antagonist, R-954, on the enhanced vascular permeability in streptozotocin (STZ)-induced diabetic Wistar rats compared with age-matched controls. Plasma extravasation was determined using Evans blue dye in selected target tissues (left and right heart atria, ventricles, lung, abdominal and thoracic aortas, liver, spleen, renal cortex and medulla), at 1 and 4 weeks following STZ administration. The vascular permeability was significantly increased in the aortas, cortex, medulla, and spleen in 1-week STZ rats and remained elevated at 4 weeks of diabetes. Both atria showed an increased vascular permeability only after 4-week STZ-administration. R-954 (2 mg/kg, bolus, s.c.), given 2 h prior to Evans blue dye, to 1- and 4-week diabetic rats significantly inhibited (by 48-100 %) plasma leakage in most tested tissues affected by diabetes with no effect in healthy rats. These results showed that the inducible bradykinin B, receptor subtype participates in the modulation of the vascular permeability in diabetic rats and suggest that selective bradykinin B, receptor antagonism could have a beneficial role in reducing diabetic vascular complications. (c) 2005 Elsevier B.V. All rights reserved.