期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 285, 期 1, 页码 R117-R124出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00476.2002
关键词
candesartan; isoprostane; angiotensin receptor blocker; PD-123,319; malonyldialdehyde
类别
资金
- NHLBI NIH HHS [HL68686-01] Funding Source: Medline
- NIDDK NIH HHS [DK-36079, DK-49870] Funding Source: Medline
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).
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