Involvement of the endothelin and nitric oxide systems in the pathogenesis of renal ischemic damage in an experimental diabetic model

LIFE SCIENCES

卷:91

Article; Proceedings Paper

Abu-Saleh, Niroz¹  Ovcharenko, Elena¹  Awad, Hoda¹  Goltsman, Ilia¹  Khamaisi, Mogher²  Hoffman, Aaron³  Heyman, Samuel N.⁴  Winaver, Joseph¹  Abassi, Zaid^1,5 

[1] Technion Israel Inst Technol, Fac Med, Dept Physiol & Biophys, IL-31096 Haifa, Israel

[2] Inst Endocrinol Diabet & Metab & Internal Med C, Haifa, Israel

[3] Dept Vasc Surg, Haifa, Israel

[4] Hadassah Hebrew Univ Hosp, Dept Med, Jerusalem, Israel

[5] Rambam Med Ctr, Res Unit, Haifa, Israel

关键词: Diabetes mellitus;    Acute kidney injury;    Ischemia reperfusion injury;    Endothelin-1;    Endothelin receptor blockers;    Nitric oxide;    Nitric oxide synthase;   

DOI  :  10.1016/j.lfs.2012.02.002

来源: Elsevier

【 摘 要 】

Aims: Ischemic acute kidney injury (iAKI) in experimental diabetes mellitus (DM) is associated with a rapid kidney dysfunction more than in non-diabetic rats. We hypothesize that this vulnerability is due to excessive endothelin-1 (ET-1) expression along with dysregulation of nitric oxide synthase (NOS) isoforms. The aim of the present study was to assess the impact of ischemia on renal function in diabetic rats as compared with non-diabetic rats, and to investigate the involvement of ET-1 and NO systems in the susceptibility of diabetic kidney to ischemic damage. Main methods: DM was induced by Streptozotocin. iAKI was induced by clamping of left renal artery for 30 min. Right intact kidney served as control. 48 h following ischemia, clearance protocols were applied to assess glomerular filtration rate (GFR), urinary flow (V) and sodium excretion (UNaV) in both kidneys. The renal effects of ABT-627, ETA antagonist; A192621.1, ETB antagonist; L-NAME, NOS non-selective inhibitor; 1400 W, inducible NOS (iNOS) inhibitor; and NPLA, neuronal NOS (nNOS) inhibitor, were assessed following ischemic renal injury in diabetic rats. Key findings: Induction of iAKI in diabetic and non-diabetic rats caused significant reductions in GFR, V, and UNaV, which were greater in diabetic than non-diabetic rats. While, treatment with ABT-627 decreased V and UNaV, and increased GFR, A192621.1 decreased all these parameters. L-NAME, 1400 W, and NPLA improved GFR in the ischemic diabetic kidney. Significance: Excessive vasoconstrictive effects of ET-1 via ETA and upregulation of iNOS, are partly responsible for the impaired recovery of renal function following ischemia in diabetic rats. (c) 2012 Elsevier Inc. All rights reserved.

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