Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression
Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression
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DOI：
10.1152/ajpregu.00476.2002
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发表时间：
2003-07-01
影响因子：
2.8
通讯作者：
Wilcox, CS
中科院分区：
文献类型：
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作者：
Chabrashvili, T;Kitiyakara, C;Wilcox, CS
氧化应激伴随血管紧张素（ANG）II输注，但ANG 1型与2型受体（分别为AT（1）-R和AT（2）-R）的作用尚不清楚。大鼠皮下注射ANG Ⅱ 1周。采用实时定量PCR检测8-异前列腺素F-2 α（8-Iso）和丙二醛（MDA）的排泄与NADPH氧化酶和超氧化物歧化酶（SOD）亚基的肾皮质mRNA丰度相关。ANG II灌注大鼠亚组给予AT（1）-R拮抗剂坎地沙坦酯（Cand）或AT（2）-R拮抗剂PD-123，319（PD）。与载体（Veh）相比，ANG II使8-Iso排泄增加41%（Veh，5.4 +/- 0.8 vs. ANG II，7.6 +/- 0.5 pg/24 h; P < 0.05）。Cand（5.6 +/- 0.5 pg/24 h; P < 0.05）阻止了这种情况，PD（15.8 +/- 2.0 pg/24 h; P < 0.005）增加了这种情况。MDA排泄量也有类似的变化。与Veh相比，ANG II显著（P < 0.005）增加肾皮质p22（phox）（2倍）、Nox-1（2.6倍）和Mn-SOD（1.5倍）的mRNA表达，降低Nox-4（2.1倍）和细胞外（EC）-SOD（2.1倍）的表达。除Mn-SOD升高外，Cand可抑制上述变化。PD加重了p22（phox）和Nox-1的变化，并增加了p67（phox）。我们的结论是，血管紧张素II输注通过AT（1）-R刺激氧化应激，增加肾皮质p22（phox）和Nox-1的mRNA表达，减少Nox-4和EC-SOD的丰度。这被AT（2）-R的强大保护作用所抵消，同时伴有p22（phox）、Nox-1和p67（phox）的表达减少。
Oxidative stress accompanies angiotensin (ANG) II infusion, but the role of ANG type 1 vs. type 2 receptors (AT(1)-R and AT(2)-R, respectively) is unknown. We infused ANG II subcutaneously in rats for 1 wk. Excretion of 8-isoprostaglandin F-2alpha (8-Iso) and malonyldialdehyde (MDA) were related to renal cortical mRNA abundance for subunits of NADPH oxidase and superoxide dismutases (SODs) using real-time PCR. Subsets of ANG II-infused rats were given the AT(1)-R antagonist candesartan cilexetil (Cand) or the AT(2)-R antagonist PD-123,319 (PD). Compared to vehicle (Veh), ANG II increased 8-Iso excretion by 41% (Veh, 5.4 +/- 0.8 vs. ANG II, 7.6 +/- 0.5 pg/24 h; P < 0.05). This was prevented by Cand (5.6 +/- 0.5 pg/24 h; P < 0.05) and increased by PD (15.8 +/- 2.0 pg/24 h; P < 0.005). There were similar changes in MDA excretion. Compared to Veh, ANG II significantly (P < 0.005) increased the renal cortical mRNA expression of p22(phox) (twofold), Nox-1 (2.6-fold), and Mn-SOD (1.5-fold) and decreased expression of Nox-4 (2.1-fold) and extracellular (EC)-SOD (2.1-fold). Cand prevented all of these changes except for the increase in Mn-SOD. PD accentuated changes in p22(phox) and Nox-1 and increased p67(phox). We conclude that ANG II infusion stimulates oxidative stress via AT(1)-R, which increases the renal cortical mRNA expression of p22(phox) and Nox-1 and reduces abundance of Nox-4 and EC-SOD. This is offset by strong protective effects of AT(2)-R, which are accompanied by decreased expression of p22(phox), Nox-1, and p67(phox).