Inducible Nitric Oxide Synthase (iNOS) is Increased in Diabetic Rat Glomeruli: Role of Angiotensin II (AII).
- Author:
Kyu Hun CHOI
1
;
Hyunjin NOH
;
Bum Seok KIM
;
Shin Wook KANG
;
Dae Suk HAN
;
Ho Yung LEE
Author Information
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. nohneph@hotmail.com
- Publication Type:Original Article
- Keywords:
Diabetic nephropathy;
Inducible nitric oxide synthase;
Angiotensin II
- MeSH:
Angiotensin II*;
Angiotensins*;
Animals;
Blood Pressure;
Blotting, Western;
Diabetic Nephropathies;
Humans;
Male;
Nitric Oxide Synthase Type II*;
Rats*;
Receptor, Angiotensin, Type 1;
RNA, Messenger;
Streptozocin;
Up-Regulation
- From:Korean Journal of Nephrology
2003;22(4):366-373
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: This study was designed to examine whether iNOS pathway is pathologically altered in experimental diabetic nephropathy and whether therapy with ACE inhibitor (imidapril: I) or angiotensin II type 1 receptor (AT1) blocker (L-158, 809: L) ameliorates these changes. METHODS: Male SD rats were injected with diluent (control: C) or streptozotocin. Diabetic (D) rats were then randomized to receive vehicle, I (2 mg/ kg/d) or L (1 mg/kg/d) by gavage. At the end of the 12-week treatment, rats underwent either a 4 hour placebo or an intraperitoneal LPS (2 mg/kg) challenge. Inducible NOS mRNA and protein were measured by RT-PCR and Western blot in isolated glomeruli. RESULTS: Systolic blood pressure and urinary protein excretion increased significantly in D rats compared with C. The basal expression of iNOS mRNA was increased in D rats compared with that of C, whereas there was no significant difference in the level of protein. Upon LPS stimulation, the iNOS mRNA and protein expression was significantly elevated in D rats. In D rats, this up-regulation of LPS-stimulated iNOS expression was equally ameliorated by both I and L in mRNA and protein levels. CONCLUSION: LPS-stimulated glomerular iNOS expression was enhanced in diabetic nephropathy, and the activation of angiotensin II may play a role in this enhancement.
