Korean J Nephrol.  2003 Jul;22(4):366-373.

Inducible Nitric Oxide Synthase (iNOS) is Increased in Diabetic Rat Glomeruli: Role of Angiotensin II (AII)

• Choi KH
• Noh H
• Kim BS
• Kang SW
• Han DS
• Lee HY

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.

Keyword

Diabetic nephropathy; Inducible nitric oxide synthase; Angiotensin II

MeSH Terms

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
Angiotensin II
Angiotensins
Nitric Oxide Synthase Type II
RNA, Messenger
Receptor, Angiotensin, Type 1
Streptozocin