SEQUENTIAL ACTIVATION OF THE REACTIVE OXYGEN SPECIES/ANGIOTENSINOGEN/RENIN–ANGIOTENSIN SYSTEM AXIS IN RENAL INJURY OF TYPE 2 DIABETIC RATS

Clinical and Experimental Pharmacology and Physiology - Tập 35 Số 8 - Trang 922-927 - 2008
Kayoko Miyata1, Naro Ohashi2, Yuki Suzaki2, Akemi Katsurada2, Hiroyuki Kobori2
1Department of Medicine, and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
2Departments of Medicine and Physiology, and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana, USA

Tóm tắt

SUMMARY The present study was performed to test the hypothesis that the reactive oxygen species (ROS)–angiotensinogen (AGT)–renin angiotensin system (RAS) axis is sequentially activated in the development of diabetic nephropathy in Zucker diabetic fatty (ZDF) obese rats. Genetic pairs of male ZDF obese and control ZDF lean rats (n = 12 of each species) were killed every 3 weeks from 12 to 21 weeks of age (n = 6 at each time point). The ZDF obese rats developed diabetes mellitus at 12 weeks. At that time, urinary excretion rates of 8‐isoprostane were similar between the groups; however, urinary 8‐isoprostane levels were significantly increased at 15 weeks in ZDF obese rats compared with controls (36 ± 6 vs 15 ± 2 ng/day, respectively). At 15 weeks, protein levels of cortical angiotensinogen were similar between groups; however, cortical angiotensinogen levels were significantly increased at 18 weeks in ZDF obese rats compared with controls (relative ratio of 2.32 ± 0.21 vs 1.00 ± 0.20, respectively). At 12 weeks, angiotensin (Ang) II‐like immunoreactivity was similar between groups in both the glomeruli and tubules; however, AngII‐like immunoreactivity was increased significantly at 21 weeks in ZDF obese rats compared with controls (relative ratios of 1.98 ± 0.55 vs 1.00 ± 0.03, respectively, for glomeruli and 1.58 ± 0.16 vs 1.00 ± 0.13, respectively, for tubules). Moreover, at 21 weeks, the desmin‐positive area in the glomeruli (0.63 ± 0.08 vs 0.22 ± 0.05%) and Masson's trichrome stain‐positive area in the interstitium (4.97 ± 0.05 vs 3.18 ± 0.41%) were significantly increased in ZDF obese rats compared with controls, even though these differences had not been observed earlier. These data suggest that the sequential activation of the ROS–AGT–RAS axis plays an important role in the development of diabetic nephropathy in ZDF obese rats.

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Clinical and Experimental Pharmacology and Physiology

Tập 35 Số 8

922-927

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