Losartan and ozagrel reverse retinal arteriolar constriction in non-obese diabetic mice
Losartan and ozagrel reverse retinal arteriolar constriction in non-obese diabetic mice
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DOI：
10.1080/10739680701829802
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发表时间：
2008-01-01
期刊：
影响因子：
2.4
通讯作者：
Harris, Norman R.
中科院分区：
文献类型：
--
作者：
Lee, Seungjun;Harris, Norman R.
目的：糖尿病早期观察到视网膜血流量减少。小静脉可能影响小动脉的收缩和血流；因此，我们假设糖尿病会诱导靠近小静脉的小动脉收缩，收缩是由血栓素和血管紧张素II介导的。方法：使用非肥胖糖尿病小鼠（NOD），在血糖水平超过200 mg/dL的年龄后三周进行视网膜测量，并对年龄匹配的正常血糖NOD小鼠进行实验。测量包括视网膜小动脉直径和红细胞速度，并在注射血栓烷合成酶抑制剂ozagrel后重复。将小鼠再分成两组，分别给予含有或不含血管紧张素II受体拮抗剂氯沙坦的饮用水。结果：高血糖小鼠视网膜小动脉收缩，血流明显减少。然而，并不是所有的小动脉都受到同样的影响；血管收缩仅限于靠近小静脉的小动脉。奥扎格雷尔（61 +/- 2 μ m）和氯沙坦（63 +/- 2 μ m）均可消除小动脉血管收缩（对照组平均小动脉直径= 51 +/- 1 μ m vs. 61 +/- 1 μ m, p < 0.01）。结论：NOD小鼠小静脉依赖性小动脉血管收缩是由血栓素和/或血管紧张素II介导的。
Objective: Reductions in retinal blood flow are observed early in diabetes. Venules may influence arteriolar constriction and flow; therefore, we hypothesized that diabetes would induce the constriction of arterioles that are in close proximity to venules, with the constriction mediated by thromboxane and angiotensin II.Methods: Using nonobese diabetic (NOD) mice, retinal measurements were performed three weeks following the age at which glucose levels exceeded 200 mg/dL, with accompanying experiments on age-matched normoglycemic NOD mice. The measurements included retinal arteriolar diameters and red blood cell velocities and were repeated following an injection of the thromboxane synthase inhibitor, ozagrel. Mice were subdivided into equal groups and given drinking water with or without the angiotensin II receptor antagonist, losartan.Results: Retinal arterioles were constricted in hyperglycemic mice, with a significant reduction in flow. However, not all arterioles were equally affected; the vasoconstriction was limited to arterioles that were in closer proximity to venules. The arteriolar vasoconstriction (mean arteriolar diameters = 51 +/- 1 vs. 61 +/- 1 mu m in controls; p < 0.01) was eliminated by both ozagrel (61 +/- 2 mu m) and losartan (63 +/- 2 mu m).Conclusions: Venule-dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II.