Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney

Epoxyeicosatrienoic acids (EETs) are major products of cytochrome P450 (CYP )-catalyzed metabolism of arachidonic acid in the kidney. The potent effect of EETs on renal vascular tone and tubular ion and water transport implica tes their role in the regulation of renal function and blood pressure. The present study was designed to test the hypothesis that CYP-catalyzed EET fo rmation was altered in the spontaneously hypertensive rat (SHR) kidney. The formation of 14,15- and 11,12-EET was similar to 2-fold higher in incubati ons of arachidonic acid with SHR renal cortical microsomes relative to micr osomes from normotensive Wistar-Kyoto (WKY) rats. This was consistent with increased expression of a CYP2J2 immunoreactive protein in the SHR cortex a nd outer medulla. In contrast, there was no significant difference in the l evels of the CYP2E and CYP2C epoxygenases in SHR and WKY kidneys. Protein a nd RNA analysis suggests that the CYP2J2 immunoreactive protein that is ove rexpressed in the SHR kidney is distinct from the known rat CYP2J isoforms. EET formation also was documented in vivo from measurements of urinary EET excretion. Importantly, the excretion rates of 14,15-, and 11,12-EETs were 2.5- and 1.8-fold higher, respectively, in SHR than WKY kidney. These stud ies provide both in vitro and in vivo evidence for increased EET formation in the SHR kidney and identify a novel CYP2J2 immunoreactive protein that i s differentially expressed in the hypertensive kidney. In light of the know n biological properties of the EETs, these findings may be important in elu cidating the mechanisms that control renal vascular tone and tubular ion tr ansport in the SHR.