Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy
Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy
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DOI：
10.1161/01.hyp.0000203826.15076.4b
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发表时间：
2006-04-01
期刊：
影响因子：
8.3
通讯作者：
Ito, S
中科院分区：
文献类型：
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作者：
Ogawa, S;Mori, T;Ito, S
我们验证了血管紧张素II型1受体阻断与尿白蛋白和IV型胶原蛋白排泄平行减少氧化应激标志物的假设。66例合并肾病的糖尿病患者随机分为血管紧张素II受体阻滞剂（ARB, n = 33）组和三氯甲肼（n = 33）组。在本研究之前，大多数患者已接受血管紧张素转换酶抑制剂或钙通道阻滞剂治疗bb0 = 1年。两组之间血压的降低没有差异，HbA1c水平在研究期间（8周）没有变化。用ARB（坎地沙坦8mg /天，n = 11或缬沙坦80mg /天，n = 22）治疗8周，降低了血浆单核细胞化学引诱蛋白1、白细胞介素6、尿8-肾上腺前列腺素F2 α、8-羟基脱氧鸟苷、白蛋白和IV型胶原蛋白的水平，而三氯甲基嗪（2mg /天）没有改变这些标志物的水平。尿8-肾上腺前列腺素F2 α和8-羟基脱氧鸟苷的减少与尿白蛋白和IV型胶原蛋白的减少有显著相关性。氧化应激大的受试者由于给药ARB有较大的降低率，并表现出较大的尿白蛋白抑制。这些结果表明，ARBs可以降低糖尿病患者的氧化应激和炎症，而不依赖于其对血压的影响。此外，血管紧张素II引起的氧化应激增加可能在糖尿病肾病的进展中起重要作用。我们的结果可能有助于解释ARB在一些患者中非常有效地减少尿白蛋白排泄的临床观察，而在其他患者中则不然。
We tested the hypothesis that blockade of angiotensin II type 1 receptors reduces oxidative stress markers in parallel with urinary albumin and type IV collagen excretions. Sixty-six diabetic patients with nephropathy were randomly assigned to either the angiotensin II receptor blocker ( ARB; n = 33) or trichlormethiazide ( n = 33) group. The majority of patients had been treated with angiotensin-converting enzyme inhibitors or calcium channel blockers for >= 1 year before the present study. Reduction of blood pressure was not different between the 2 groups, and HbA1c levels did not change over the study period ( 8 weeks). Treatment with ARB ( candesartan 8 mg/day, n = 11 or valsartan 80 mg/day, n = 22) for 8 weeks reduced the levels of plasma monocyte chemoattractant protein 1, interleukin 6, urinary 8-epi-prostaglandin F2 alpha, 8-hydroxydeoxyguanosine, albumin, and type IV collagen, whereas the levels of these markers were not altered with trichlormethiazide ( 2 mg/day). Significant correlation was observed between the reduction of the urinary 8-epi-prostaglandin F2 alpha and 8-hydroxydeoxyguanosine and those of the urinary albumin and type IV collagen. Subjects with large oxidative stress had large reduction rates because of ARB administration and showed large urinary albumin suppression. These results suggest that ARBs reduce oxidative stress and inflammation in diabetic patients independent of their effects on blood pressure. In addition, increases in oxidative stress caused by angiotensin II may play an important role in the progression of diabetic nephropathy. Our results may help to explain the clinical observation that ARB reduces urinary albumin excretion very efficiently in some patients but not in others.