title: Free radical scavenging decreases endothelin-1 excretion and glomerular albumin permeability during type 1 diabetes.
abstract: Increased renal endothelin-1 (ET-1) production and an ETAreceptor-dependent increase in glomerular albumin permeability (Palb) accompany type 1 diabetes mellitus (T1D). We hypothesized that T1D-induced oxidative stress contributes to renal ET-1 production and glomerular PalbMale rats with streptozotocin-induced T1D were provided free access to drinking water without additives (T1D rats) or containing the free radical scavenger tempol (1 mmol/L; T1D+Tempol). After 3 weeks, T1D+Tempol rats displayed lower urinary excretion of thiobarbituric acid reactive substances and glomerular superoxide production (dihydroethidium staining) compared to T1D rats. Urinary ET-1 excretion and inner medullary (but not cortical or outer medullary) prepro-ET-1 mRNA expression were lower in the T1D+Tempol group than in the T1D group. Palb, measured as the change in volume of isolated glomeruli upon exposure to oncotic gradients of albumin, was significantly lower in the T1D+Tempol group than in the T1D group. Tempol treatment did not alter protein excretion or creatinine clearance. These data support the postulate that oxidative stress contributes to glomerular Palband renal ET-1 production during the early phase of type 1 diabetes.
authors.affiliation: Medical College of Georgia, Augusta University, Augusta, Georgia.|Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Saleh
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Miguel
authors.affiliation: Medical College of Georgia, Augusta University, Augusta, Georgia.
authors.forename: David I
authors.initials: DI
authors.lastname: Stevens
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Carmines
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.|Medical College of Georgia, Augusta University, Augusta, Georgia.
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama jenniferpollock@uabmc.edu.|Medical College of Georgia, Augusta University, Augusta, Georgia.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pollock
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D003497:Cyclic N-Oxides / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D019332:Endothelin-1 / Q000652:urine*; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013311:Streptozocin
chemical_list: D000418:Albumins; D003497:Cyclic N-Oxides; D019332:Endothelin-1; D016166:Free Radical Scavengers; D013113:Spin Labels; D013311:Streptozocin; C001803:tempol
keywords: Diabetes; ET‐1; glomerular permeability; tempol