Epoxyeicosatrienoic
acids (EETs) are
arachidonic acid metabolites synthesized by
cytochrome P450 epoxygenases.
Biological activities for EETs include vasodilation, decreasing
inflammation, opposing apoptosis, and inhibiting renal
sodium reabsorption. These actions are beneficial in lowering blood pressure and slowing
kidney disease progression. Furthermore, evidence in human and experimental animal studies have found that decreased EET levels contribute to
hypertension and
kidney diseases. Consequently, EET mimics/analogs have been developed as a potential therapeutic for
hypertension and acute and
chronic kidney diseases. Their development has resulted in EET analogs that are orally active with favorable pharmacological profiles. Analogs for
8,9-EET,
11,12-EET, and
14,15-EET have been tested in several
hypertension and
kidney disease animal models. More recently, kidney targeted EET analogs have been synthesized and tested against
drug-induced nephrotoxicity. Experimental evidence has demonstrated compelling therapeutic potential for EET analogs to oppose cardiovascular and
kidney diseases. These EET analogs lower blood pressure, decrease kidney
inflammation, improve vascular endothelial function, and decrease kidney
fibrosis and apoptosis. Overall, these preclinical studies support the likelihood that EET analogs will advance to clinical trials for
hypertension and associated comorbidities or acute and
chronic kidney diseases.