Inducible nitric oxide synthase (iNOS) expression in early diabetic nephropathy: Effect of ACE inhibitor and angiotensin II receptor antagonists

Öz

Amaç: Diabetes mellitusun en önemli komplikasyonlarından biri diabetik nefropatidir. Kaptopril bir ACE inhibitörüdür ve diabetik nefropati tedavisinde kullanılır. Son yıllarda anjiotensin reseptör antagonistlerinin proteinüriyi önlemek için ACE inhibitörleri gibi etki ettikleri gösterilmiştir. Anjiotensin II-AT1 reseptör antagonisti Losartan, bu çalışma alanında çalışılan yeni bir antihipertansif materyaldir. Nitrik oksit (NO), akut streptozosin verilerek oluşturulan diabetteki, akut meydana gelen hemodinamik Materials and methods: 32 male Wistar rats weighting 140-220 g were used for this study. The rats were made diabetic using a single intraperitoneal injection of 65 mg/kg streptozotocin (Sigma Chemical Co., St. Louis, MO, USA). Rats were divided in to four groups: Group A (n= 8): Control, Group B (n=8): STZ- diabetic control, Group C (n=8): STZ + Losartan (DM+ L) (10 mg/kg/day), Group D (n=8): STZ + Captopril (DM+C) (50 mg/kg/day). The experiment lasted 6 weeks. The levels of blood glucose, albuminuria, creatinine clearence was determined. Renal tissue samples were extracted under anesthesia for histopathologic study. Monoclonal antibodie against the following antigen was used: iNOS . Result: At the diabetic control group, the level of albuminuria was increased significantly and was decreased significantly in the Captopril and Losartan given groups (p<0.001). There was no statistically significant differences in albuminuria between the DM+L and DM+C groups (p>0.05). The values of creatinine clearence were increased in diabetic control group as compared to control group (p<0.001). The reducing creatinine clearence in DM+L and DM+C groups was statistically not significant (p>0.05). By immunohistochemistry, iNOS staining was only observed in glomeruli of diabetic control group. Conclusion: Glomerular iNOS expression was enhanced in diabetic nephropathy and the activation of angiotensin II may play a role in this enhancement. Materyal ve metod: Bu çalışmada 140-220 gr ağırlığında 32 adet Wistat ratları kullanılmıştır. Ratlarda tek doz intraperitoneal 65 mg/kg streptozotocin (Sigma Chemical Co., St. Loui, MO, USA) kullanılarak diabet oluşturulmuştur. Ratlar 4 gruba bölünmüştür: grup A (n=8): Kontrol, grup B (n=8): STZ-diabetik kontrol, grup C (n=8): STZ+Losartan (DM+L) (10 mg/kg/gün), grup D (n=8): STZ+Kaptopril (DM+C) (50 mg/kg/gün). Deney 6 hafta sürdürüldü. Kan şekeri düzeyi, albüminüri, kreatinin kleransı saptandı. Böbrek dokusu örnekleri histopatolojik çalışma için anestezi altında alındı. Monoklonal antikora karşı antijen kullanıldı: iNOS . Sonuçlar: Diabetik kontrol grubunda albiminüri seviyesi anlamlı derecede artmış ve Kaptopril ve Losartan verilen gruplarda önemli derecede azalmıştı (p<0.001). DM+L ve DM+C grupları arasında anlamlı bir istatiksel fark görülmemişti (p>0.05). Kreatinin kleransinin değeri kontrol grubuna benzer şekilde diabetik kontrol grubunda da artmıştı (p<0.001). DM+L ve DM+C gruplarında kreatinin kleransinindeki azalma istatiksel olarak anlamlı değildi (p>0.05). İmmün dokukimyasal olarak iNOS boyanması diabetik kontrol grubunda sadece glomerüllerde görüldü. Tartışma: Glomerüler iNOS ekspresyonu diabetik nefropatiyi arttırır ve anjiotensin II aktivasyonu bu artmada rol oynayabilir

Anahtar Kelimeler

• iNOS, diabetik nefropati, ACE inhibitörleri, Anjiotensin II

Erken diabetik nefropatide indüklenebilir nitrik oksid sentetaz (iNOS) ekspresyonu: ACE inhibitörlerinin ve anjiotensin II reseptör antagonistlerinin etkileri

Abstract

Objective: One of the most important complications of diabetes mellitus is diabetic nephropathy. Captopril is an ACE inhibitor and used in the diabetic nephropathy treatment. In the last years, it has been shown that angiotensin receptor antagonists have similar efficiency as ACE inhibitors for prevention of proteinuria. The angiotensin II-AT1 receptor antagonist Losartan is a new antihypertansive material that has been worked on this field. Nitric oxide (NO) is a multifunctional mediator that has been implicated in the short-term hemodynamic alterations that occur acute streptozocin induced değişikliklerde etkisi bulunan çok fonksiyonlu bir mediadiabetes. Nitric oxide is synthesized exclusively from its tördür. Nitrik oksit, nitrik oksit sentez (NOS) enziminin precursor L-arginine under the catalytic effect of nitric oxide synthase (NOS), which there are three isoforms. Diabetic nephropathy represents a complex metabolic arena characterized with patho-physiological events that both stimulate end depress intrarenal NO production. The aim of this study was to assess whether the iNOS pathway is pathologically altered in experimental diabetic nephropathy, and in therapy with ACE inhibitor (Captopril) or angiotensin II-AT1 receptor antagonist (Losartan). Materials and methods: 32 male Wistar rats weighting 140-220 g were used for this study. The rats were made diabetic using a single intraperitoneal injection of 65 mg/kg streptozotocin (Sigma Chemical Co., St. Louis, MO, USA). Rats were divided in to four groups: Group A (n= 8): Control, Group B (n=8): STZ- diabetic control, Group C (n=8): STZ + Losartan (DM+ L) (10 mg/kg/day), Group D (n=8): STZ + Captopril (DM+C) (50 mg/kg/day). The experiment lasted 6 weeks. The levels of blood glucose, albuminuria, creatinine clearence was determined. Renal tissue samples were extracted under anesthesia for histopathologic study. Monoclonal antibodie against the following antigen was used: iNOS . Result: At the diabetic control group, the level of albuminuria was increased significantly and was decreased significantly in the Captopril and Losartan given groups (p<0.001). There was no statistically significant differences in albuminuria between the DM+L and DM+C groups (p>0.05). The values of creatinine clearence were increased in diabetic control group as compared to control group (p<0.001). The reducing creatinine clearence in DM+L and DM+C groups was statistically not significant (p>0.05). By immunohistochemistry, iNOS staining was only observed in glomeruli of diabetic control group. Conclusion: Glomerular iNOS expression was enhanced in diabetic nephropathy and the activation of angiotensin II may play a role in this enhancement

Keywords

• iNOS, diabetic nephropathy, ACE inhibitor

Kaynakça

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29. Addres for correspondence
30. Kısmet Bildirici, MD
31. Akarbaşı Mah. Arısoy Sok. Ayseana Sitesi No:19 B Blok D:8 Eskisehir/ Turkey
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