Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive Dahl salt-sensitive rat. Hypertension 2013 Nov;62(5):905-13
Date
08/28/2013Pubmed ID
23980070Pubmed Central ID
PMC3872985DOI
10.1161/HYPERTENSIONAHA.113.01949Scopus ID
2-s2.0-84886393761 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
Salt-sensitive hypertension leads to kidney injury. The Dahl salt-sensitive hypertensive rat (Dahl SS) is a model of salt-sensitive hypertension and progressive kidney injury. The current set of experimental studies evaluated the kidney protective potential of a novel epoxyeicosatrienoic acid analog (EET-B) in Dahl SS hypertension. Dahl SS rats receiving high-salt diet were treated with EET-B (10 mg/kg per day) or vehicle in drinking water for 14 days. Urine, plasma, and tissue samples were collected at the end of the treatment protocol to assess kidney injury, oxidative stress, inflammation, and endoplasmic reticulum stress. EET-B treatment in Dahl SS rats markedly reduced urinary albumin and nephrin excretion by 60% to 75% along with 30% to 60% reductions in glomerular injury, intratubular cast formation, and kidney fibrosis without affecting blood pressure. In Dahl SS rats, EET-B treatment further caused marked reduction in oxidative stress with 25% to 30% decrease in kidney malondialdehyde content along with 42% increase of nitrate/nitrite and a 40% reduction of 8-isoprostane. EET-B treatment reduced urinary monocyte chemoattractant protein-1 by 50% along with a 40% reduction in macrophage infiltration in the kidney. Treatment with EET-B markedly reduced renal endoplasmic reticulum stress in Dahl SS rats with reduction in the kidney mRNA expressions and immunoreactivity of glucose regulatory protein 78 and C/EBP homologous protein. In summary, these experimental findings reveal that EET-B provides kidney protection in Dahl SS rats by reducing oxidative stress, inflammation, and endoplasmic reticulum stress, and this protection was independent of reducing blood pressure.
Author List
Hye Khan MA, Neckár J, Manthati V, Errabelli R, Pavlov TS, Staruschenko A, Falck JR, Imig JDMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Eicosanoids
Endoplasmic Reticulum Stress
Human Umbilical Vein Endothelial Cells
Humans
Hypertension
Inflammation
Kidney
Kidney Diseases
Oxidative Stress
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary