Angiotensin II Receptor Blockers Inhibit the Generation of Epoxyeicosatrienoic Acid from Arachidonic Acid in Recombinant<scp>CYP</scp>2C9,<scp>CYP</scp>2J2 and Human Liver Microsomes

Abstract

Abstract Cytochrome P450 ( CYP ) 2C9, CYP 2C8 and CYP 2J2 enzymes, which metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids, have cardioprotective effects including anti‐inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers ( ARB s) may inhibit AA metabolism via CYP 2C8. Using recombinant CYP 2C9, CYP 2J2 and human liver microsomes ( HLM s), the aim was now to compare the ability of six different clinically used ARB s to inhibit AA metabolism in vitro . The rank order of the ARB s for the 50% inhibitory concentration ( IC 50 ) of AA metabolism was losartan &lt;telmisartan &lt;irbesartan &lt;candesartan &lt;olmesartan &lt;valsartan via CYP 2C9, and telmisartan &lt;irbesartan &lt;olmesartan &lt;losartan &lt;candesartan and valsartan via CYP 2J2. The order for the HLM s was losartan &lt;telmisartan &lt;irbesartan &lt;olmesartan &lt;candesartan &lt;valsartan. Some ARB s having lower concentration of IC 50 indicate that these ARB s might inhibit the AA metabolism in the liver.