Blood Pressure Control and Hypertension

20-HETE was proposed based on (a) P450 inhibitor studies, and their effects on tubular Na transport , (b) differences between DS and DR rats in CYP4A expression and 20-HETE synthase activity and (c) normalization of Cl transport in DS rats by 20-HETE  

The inhibition of distal nephron Na reabsorption by 5,6-EET the induction of kidney CYP2C23 and EET biosynthesis by excess dietary salt 123 and EET-induced dilation of micro-circulatory beds suggested antihypertensive functions for the EETs In agreement with this (a) clotrimazole inhibition of the rat kidney epoxygenases caused reductions in renal EET biosynthesis , and the development of clotrimazole-dependent, salt-sensitive hypertension , (b) high salt diets failed to induce the activity of the kidney AA epoxygenase in hypertensive DS rats , and (c) the EETs contribute to the prostanoid- and NO-independent dilation pf renal afferent arterioles In summary, 

57 mm of Hg, respectively, and caused parallel increases in 20-HETE biosynthesis and in the kidney levels of CYP4A8 mRNAs.  

The studies of the P450 AA monooxygenase have uncovered new and important roles for P450 in the metabolism of endogenous substrates, and added P450 to the list of enzymes that participate in the metabolism of AA, a fatty acid that serves 

None of the studies carried out in the authors laboratory could have been possible without the continuous and generous grant support from NIGMS and NIDDK. 

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