ISSN: 2161-1017
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Zaid Abassi
Accepted Abstracts: Endocrinol Metab Synd
Introduction: 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. Aims: To assess the impact of ischemia on renal function in diabetic rats 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. 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 hrs 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, an ETA antagonist; A192621.1, an ETB antagonist; L-NAME, a non-selective inhibitor of endothelial NOS (eNOS); 1400W, an inducible NOS (iNOS) inhibitor; and NPLA, a neuronal NOS (nNOS) inhibitor, were assessed following ischemic renal injury in diabetic rats. Results: 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, 1400W, 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.
Zaid Abassi has completed his PhD at the age of 29 years from The Technion, Israeli Institute of Technology and postdoctoral studies from National Institutes at Health, Bethesda Maryland. He is the director of the laboratory for Renal Research and Hypertension, Faculty of Medicine, Technion. He has published more than 130 papers in reputed journals and serving as a reviewer for over 30 prestigious journals. His main research interests: 1-Mechanisms of sodium/water retention and cardiac hypertrophy in congestive heart failure; 2-Involvement of the endothelin and nitric oxide systems in the pathogenesis of cardiovascular and metabolic diseases; 3-Pathogenesis of proteinuria in experimental models of nephrotic syndrome: Novel therapeutic approaches; 4. Acute kidney injury-Pathogenesis, detection and therapy