Renal angiotensin II AT2 receptors promote natriuresis in streptozotocin-induced diabetic rats
Renal angiotensin II AT2 receptors promote natriuresis in streptozotocin-induced diabetic rats
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DOI：
10.1152/ajprenal.00092.2005
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发表时间：
2006-02-01
影响因子：
4.2
通讯作者：
Hussain, T
中科院分区：
文献类型：
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作者：
Hakam, AC;Siddiqui, AH;Hussain, T
血管紧张素II AT(2)受体被认为在病理条件下对肾脏/心血管功能起调节作用。本研究旨在探讨AT2受体在链脲佐菌素(STZ)诱导的糖尿病大鼠肾钠排泄和皮质膜AT2受体表达中的作用。与对照组相比，STZ治疗组大鼠体重显著减轻，血糖升高，血浆胰岛素水平降低。STZ诱导的糖尿病大鼠基础尿流量、尿钠排泄率(U(Na)V)、尿钠排泄分数和尿cGMP均显著高于对照组。血管紧张素Ⅱ受体拮抗剂PD-123319使链脲佐菌素诱导的糖尿病大鼠U(Na)V显著降低(1+/-0.09vs.0.45+/-0.1vs.0.4+/-0.07)。U(Na)V的降低与STZ诱导的糖尿病大鼠(21+/-2vs.10+/-0.8)尿cGMP水平(pmo1/min)显著降低有关，而在对照组(11.75+/-3vs.12.6+/-2)无明显变化。注射PD-123319对肾小球滤过率(STZ：0.30+/-0.02vs.0.25+/-0.03；对照组：1.4ml/-0.05vs.1.5+/-0.09ml/分)或平均动脉压(STZ：82+/-3vs.79+/-3.5；对照组：90+/-4vs.89+/-4毫米汞柱)没有改变，这表明该药物具有管状效应。使用AT2受体抗体的Western印迹分析显示，与对照组相比，STZ诱导的糖尿病大鼠刷状缘(类似于50倍)和基侧膜(类似于80倍)AT2受体蛋白(类似于45 kDa)的表达显著增强。综上所述，我们的数据表明糖尿病大鼠肾小管AT2受体显著增强，并可能通过cGMP途径促进这种糖尿病模型的钠排泄。
Angiotensin II AT(2) receptors have been implicated to play a role in the regulation of renal/cardiovascular functions under pathological conditions. The present study is designed to investigate the function of the AT2 receptors on renal sodium excretion and AT2 receptor expression in the cortical membranes of streptozotocin ( STZ)- induced diabetic rats. The STZ treatment led to a significant weight loss, hyperglycemia, and decrease in plasma insulin levels compared with control rats. STZ-induced diabetic rats had significantly elevated basal urine flow, urinary sodium excretion rate (U(Na)V), urinary fractional sodium excretion, and urinary cGMP compared with control rats. Infusion of PD-123319, an AT2 receptor antagonist, caused a significant decrease in U(Na)V (mu mol/ min) in STZ-induced diabetic rats (1 +/- 0.09 vs. 0.45 +/- 0.1) but not in control rats (0.35 +/- 0.05 vs. 0.4 +/- 0.07). The decrease in U(Na)V was associated with a significant decrease in urinary cGMP levels (pmol/min) in STZ-induced diabetic rats (21 +/- 2 vs. 10 +/- 0.8) but not in control rats (11.75 +/- 3 vs. 12.6 +/- 2). The infusion of PD-123319 did not alter glomerular filtration rate ( STZ: 0.3 +/- 0.02 vs. 0.25 +/- 0.03; control: 1.4 +/- 0.05 vs. 1.5 +/- 0.09 ml/min) or mean arterial pressure (STZ: 82 +/- 3 vs. 79 +/- 3.5; control: 90 +/- 4 vs. 89 +/- 4 mmHg), suggesting a tubular effect of the drug. Western blot analysis using an AT2 receptor antibody revealed a significantly enhanced expression of the AT2 receptor protein (similar to 45 kDa) in brush-border (similar to 50- fold) and basolateral membranes (similar to 80-fold) of STZ-induced diabetic compared with control rats. In conclusion, our data suggest that the tubular AT2 receptors in diabetic rats are profoundly enhanced and possibly via a cGMP pathway promote sodium excretion in this model of diabetes.