title: High-salt diet blunts renal autoregulation by a reactive oxygen species-dependent mechanism.
abstract: High dietary salt is common in Western countries and is an important contributor to increased cardiovascular disease. Autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) is an essential function of the renal microcirculation that could be affected by excessive dietary salt. High salt (HS) increases renal ROS generation partly by the enzyme NADPH oxidase. We hypothesized that a HS diet would impair autoregulation via NADPH oxidase-dependent ROS generation. The role of NADPH-dependent ROS production on the blunted autoregulatory response with a HS diet was assessed in vitro and in vivo using the blood-perfused juxtamedullary nephron preparation and anesthetized rats, respectively. The increase in renal lipid peroxidation and p67(phox) expression induced by HS was prevented by apocynin treatment. Control afferent arterioles exhibited normal autoregulatory behavior in response to acute increases in renal perfusion pressure, whereas arterioles from HS rats exhibited a blunted response. Autoregulatory behavior in HS rats was restored in vitro by acute exposure to the NADPH oxidase inhibitor apocynin. At the whole kidney level, in vivo experiments showed that both RBF and GFR declined in HS rats when left kidney renal perfusion pressure was reduced from ambient to 95 mmHg, whereas control rats maintained stable GFR and RBF consistent with efficient autoregulatory behavior. Apocynin treatment improved in vivo autoregulatory behavior in HS rats and had no detectable effect in normal salt diet-fed rats. These data support the hypothesis that impaired renal autoregulatory behavior in rats fed a HS diet is mediated by NADPH oxidase-derived ROS.
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Fellner
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Cook
authors.affiliation: Section of Experimental Medicine, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Connor
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and.
authors.forename: Shali
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Section of Experimental Medicine, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.affiliation: Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; and einscho@gru.edu.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Inscho
mesh_terms: D000821:Animal Feed; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D012982:Sodium, Dietary; D019255:NADPH Oxidases
keywords: 4-hydroxy-2-nonenal; afferent arterioles; apocynin; glomerular filtration rate; oxidative stress