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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice.
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Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice.

机译:新型缓激肽B1受体拮抗剂R-954对1型糖尿病小鼠血管通透性的抑制作用。

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摘要

The morbidity and mortality associated with type 1 diabetes are essentially related to the micro- and macrovascular complications that develop over time and lead to several diabetic complications, including hypertension, atherosclerosis, and retinopathy, as well as coronary and renal failure. Normally absent in physiological conditions, the bradykinin B1 receptor (BKB1-R) was recently found to be overexpressed in pathological conditions, including type 1 diabetes. In the present study, we evaluated the effect of the new BKB1-R antagonist, R-954 (Ac-Orn-[Oic2, alpha-MePhe5, D-betaNal7, Ile8]desArg9-bradykinin, on the increase in vascular permeability in streptozotocin (STZ)-diabetic mice. The capillary permeability to albumin was measured by quantifying the extravasation of albumin-bound Evans blue dye in selected target tissues (liver, pancreas, duodenum, ileum, spleen, heart, kidney, stomach, skin, muscle, and thyroid gland). Acute single administration of R-954 (300 microg/kg, i.v.) to type 1 diabetic mice 4 weeks after STZ significantly inhibited the enhanced vascular permeability in most tissues. These data provide further experimental evidence for the implication of BKB1-R in the enhanced vascular permeability associated with type 1 diabetes.
机译:与1型糖尿病相关的发病率和死亡率基本上与随时间发展的微血管和大血管并发症相关,并导致多种糖尿病并发症,包括高血压,动脉粥样硬化和视网膜病变以及冠心病和肾功能衰竭。通常在生理条件下不存在,缓激肽B1受体(BKB1-R)最近被发现在包括1型糖尿病在内的病理条件下过表达。在本研究中,我们评估了新型BKB1-R拮抗剂R-954(Ac-Orn- [Oic2,alpha-MePhe5,D-betaNal7,Ile8] desArg9-缓激肽对链脲佐菌素中血管通透性增加的影响(STZ)糖尿病小鼠,通过量化结合在选定目标组织(肝脏,胰腺,十二指肠,回肠,脾脏,心脏,肾脏,胃,皮肤,肌肉, STZ后4周向1型糖尿病小鼠急性单次施用R-954(300微克/千克,静脉注射)可显着抑制大多数组织中血管通透性的增强,这些数据为BKB1的意义提供了进一步的实验证据。 -R与1型糖尿病相关的血管通透性增加。

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