당뇨병성 신증을 유발한 백서 사구체에서 Inducible Nitric Oxide Synthase (iNOS)의 변화와 안지오텐신 전환효소 억제제 (ACEI) 및 안지오텐신 Ⅱ 1형 수용체 (AT1) 차단제 (ARB)의 효과

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 (ATI) 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 ㎎/㎏/d) or (1 ㎎/㎏/d) by gavage. At the end of the 12-week treatment, rats underwent either a 4 hour placebo or an intraperitoneal LPS (2 ㎎/㎏) 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 increas 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-stimulate glomerular iNOS expression was enhanced in diabetic nephropathy, and the activation of angiotensin Ⅱ may play a role in this enfancement.