Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive dahl salt-sensitive rat

Md Abdul Hye Khan, Jan Neckář, Vijay Manthati, Ramu Errabelli, Tengis S. Pavlov, Alexander Staruschenko, J R Falck, John D. Imig

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalHypertension
Volume62
Issue number5
DOIs
StatePublished - Nov 2013

Fingerprint

Inbred Dahl Rats
Kidney
Acids
Wounds and Injuries
Endoplasmic Reticulum Stress
8-epi-prostaglandin F2alpha
Oxidative Stress
Salts
Hypertension
Transcription Factor CHOP
Blood Pressure
Inflammation
Chemokine CCL2
Therapeutics
Clinical Protocols
Nitrites
Protein C
Malondialdehyde
Drinking Water
Nitrates

Keywords

  • arachidonate epoxygenase
  • glomerular necrosis
  • hypertension
  • inflammation
  • oxidative stress

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

Hye Khan, M. A., Neckář, J., Manthati, V., Errabelli, R., Pavlov, T. S., Staruschenko, A., ... Imig, J. D. (2013). Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive dahl salt-sensitive rat. Hypertension, 62(5), 905-913. https://doi.org/10.1161/HYPERTENSIONAHA.113.01949

Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive dahl salt-sensitive rat. / Hye Khan, Md Abdul; Neckář, Jan; Manthati, Vijay; Errabelli, Ramu; Pavlov, Tengis S.; Staruschenko, Alexander; Falck, J R; Imig, John D.

In: Hypertension, Vol. 62, No. 5, 11.2013, p. 905-913.

Research output: Contribution to journalArticle

Hye Khan, MA, Neckář, J, Manthati, V, Errabelli, R, Pavlov, TS, Staruschenko, A, Falck, JR & Imig, JD 2013, 'Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive dahl salt-sensitive rat', Hypertension, vol. 62, no. 5, pp. 905-913. https://doi.org/10.1161/HYPERTENSIONAHA.113.01949
Hye Khan, Md Abdul ; Neckář, Jan ; Manthati, Vijay ; Errabelli, Ramu ; Pavlov, Tengis S. ; Staruschenko, Alexander ; Falck, J R ; Imig, John D. / Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in hypertensive dahl salt-sensitive rat. In: Hypertension. 2013 ; Vol. 62, No. 5. pp. 905-913.
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abstract = "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.",
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AU - Errabelli, Ramu

AU - Pavlov, Tengis S.

AU - Staruschenko, Alexander

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N2 - 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.

AB - 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.

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KW - inflammation

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