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.