Kopkan_2012_Kidney.Blood.Press.Res_35_595

Objective The present study was performed to examine whether the blood pressure BP)-lowering effects of soluble epoxide hydrolase sEH inhibition in two-kidney one-clip 2K1C Goldblatt hypertension are nitric oxide NO dependent Methods Mice lacking the endothelial NO synthase eNOS gene eNOS and their wild-type controls eNOS underwent clipping of one renal artery BP was monitored by radiotelemetry and the treatment with the sEH inhibitor cis-4-[4-(3-adamantan-1-yl-ureido)cyclohex-yloxy]-benzoic acid c-AUCB was initiated on day 25 after clipping and lasted for 14 days Renal concentrations of epoxyeicosatrienoic acids EETs and their inactive metabolite dihydroxyeicosatrienoic acids DHETs were measured in the nonclipped kidney Renal NO synthase NOS activity was determined by measuring the rate of formation of L-[(14)C]citruline from L-[(14)C]arginine Results Treatment with the sEH inhibitor elicited similar BP decreases that were associated with increases in daily sodium excretion in 2K1C eNOS as well as 2K1C eNOS mice In addition treatment with the sEH inhibitor increased the ratio of EETs/DHETs in the nonclipped kidney of 2K1C eNOS as well as 2K1C eNOS mice Treatment with the sEH inhibitor did not alter renal NOS activity in any of the experimental groups Conclusions Collectively our present data suggest that the BP-lowering effects of chronic sEH inhibition in 2K1C mice are mainly associated with normalization of the reduced availability of biologically active EETs in the nonclipped kidney and their direct natriuretic actions.