title: Renal overexpression of atrial natriuretic peptide and hypoxia inducible factor-1α as adaptive response to a high salt diet.
abstract: In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis.
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina ; Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, UBA, Junín 956, Piso 5, 1113 Buenos Aires, Argentina.
authors.forename: Silvana Lorena
authors.initials: SL
authors.lastname: Della Penna
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carranza
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Elsa
authors.initials: E
authors.lastname: Zotta
authors.affiliation: Department of Pharmacology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Gorzalczany
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Carolina Susana
authors.initials: CS
authors.lastname: Cerrudo
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Natalia Lucía
authors.initials: NL
authors.lastname: Rukavina Mikusic
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Correa
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Trida
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
authors.forename: Jorge Eduardo
authors.initials: JE
authors.lastname: Toblli
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: María Inés
authors.identifier: 0000-0002-4985-2752
authors.initials: MI
authors.lastname: Rosón
authors.affiliation: Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Argentina.
authors.forename: Belisario Enrique
authors.initials: BE
authors.lastname: Fernández
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017673:Sodium Chloride, Dietary; D053773:Transforming Growth Factor beta1; D009320:Atrial Natriuretic Factor; D012964:Sodium