Biosynthesis of 20-HETE from arachidonic acid by the cytochrome P450 4A (CYP450 4A) isoforms is an important component of vascular homeostasis, especially in renal circulation. DDMS is a mechanism-based, irreversible inhibitor that has about 10-fold selectivity for the CYP4A2 enzyme which predominantly synthesizes 20-HETE in the mammalian kidney. DDMS administration in whole anesthetized rats (10 mg/kg) largely ablates the hypotension and vasodilation induced by nitric oxide donors such as NONOates.
