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 (10 mg/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.