Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury

Md Abdul Hye Khan, J R Falck, Vijaya L. Manthati, William B. Campbell, John D. Imig

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

Original languageEnglish (US)
Article number216
JournalFrontiers in Pharmacology
Volume5
Issue numberSEP
DOIs
StatePublished - Jan 1 2014

Keywords

  • Angiotensin II
  • Endothelial function
  • Epoxyeicosatrienoic acid analog
  • Mesenteric artery
  • Renal inflammation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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