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

Autor: Mogher Khamaisi, Samuel N. Heyman, Niroz Abu-Saleh, Hoda Awad, Aaron B. Hoffman, Zaid Abassi, Joseph Winaver, Elena Ovcharenko, Ilia Goltsman
Rok vydání: 2011
Předmět:
Male
medicine.medical_specialty
Ischemia
Renal function
Nitric Oxide Synthase Type II
Nitric Oxide
General Biochemistry
Genetics and Molecular Biology
Streptozocin
Endothelin receptor blockers
Nitric oxide
Diabetes Mellitus
Experimental
Rats
Sprague-Dawley
Pharmacology
Toxicology and Pharmaceutics(all)
chemistry.chemical_compound
Diabetes mellitus
Internal medicine
medicine
Animals
General Pharmacology
Toxicology and Pharmaceutics
Kidney
biology
Endothelin-1
Biochemistry
Genetics and Molecular Biology(all)
business.industry
Nitric oxide synthase
Acute kidney injury
General Medicine
Acute Kidney Injury
medicine.disease
Receptor
Endothelin A
Rats
Up-Regulation
medicine.anatomical_structure
Endocrinology
chemistry
Vasoconstriction
Reperfusion Injury
biology.protein
business
Endothelin receptor
Ischemia reperfusion injury
Glomerular Filtration Rate
Zdroj: Life sciences. 91(13-14)
ISSN: 1879-0631
Popis: 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.
Databáze: OpenAIRE
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