title: Transforming growth factor-β mediates endothelial dysfunction in rats during high salt intake.
abstract: Endothelial dysfunction has been shown to be predictive of subsequent cardiovascular events and death. Through a mechanism that is incompletely understood, increased dietary salt intake promotes endothelial dysfunction in healthy, salt-resistant humans. The present study tested the hypothesis that dietary salt-induced transforming growth factor (TGF)-β promoted endothelial dysfunction and salt-dependent changes in blood pressure (BP). Sprague-Dawley rats that received diets containing 0.3% NaCl [low salt (LS)] or 8.0% NaCl [high salt (HS)] were treated with vehicle or SB-525334, a specific inhibitor of TGF-β receptor I/activin receptor-like kinase 5, beginning on day 5. BP was monitored using radiotelemetry in four groups of rats (LS, LS + SB-525334, HS, and HS + SB-525334) for up to 14 days. By day 14 of the study, mean daytime systolic BP and mean pulse pressure of the HS group treated with vehicle was greater than those in the other three groups; mean daytime systolic BP and pulse pressure of the HS + SB-525334 group did not differ from the LS and LS + SB-525334-treated groups. Whereas mean systolic BP, mean diastolic BP, and mean arterial pressure did not differ among the groups on the seventh day of the study, endothelium-dependent vasorelaxation was impaired specifically in the HS group; treatment with the activin receptor-like kinase 5 inhibitor prevented the dietary HS intake-induced increases in phospho-Smad2 (Ser(465/467)) and NADPH oxidase-4 in endothelial lysates and normalized endothelial function. These findings suggest that HS-induced endothelial dysfunction and the development of salt-dependent increases in BP were related to endothelial TGF-β signaling.
authors.affiliation: Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Wenguang
authors.initials: W
authors.lastname: Feng
authors.affiliation: Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Ying
authors.affiliation: Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Kristal J
authors.initials: KJ
authors.lastname: Aaron
authors.affiliation: Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Veterans Affairs Medical Center, Birmingham, Alabama psanders@uab.edu.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sanders
mesh_terms: D000821:Animal Feed; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004435:Eating / Q000502:physiology; D004727:Endothelium / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism* / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D012965:Sodium Chloride; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625843:Tgfbr1 protein, rat
keywords: dietary salt; endothelial dysfunction; endothelium; hypertension; transforming growth factor-β