Role of cytochrome P450 epoxygenase-dependent arachidonic acid metabolites in kidney physiology and diseases.

Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti-hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.