Localization of the CYP4A Enzymes that Produce 20-HETE and the 20-HETE Receptor in the Brain

20‐HETE is an arachidonic acid metabolite that is catalyzed by cytochrome P450 (CYP) enzymes of the 4A and 4F families. 20‐HETE is a potent vasoconstrictor that plays an important role in the regulation of cerebral vascular function. Numerous human studies have found that inactivating mutations in the enzymes that produce 20‐HETE are associated with hypertension, stroke, and dementia. Our group previously reported that the Dahl salt‐sensitive (SS) rat also has decreased 20‐HETE levels and exhibits impaired autoregulation of cerebral blood flow and loss of cognitive function following the development of hypertension. A G‐protein coupled receptor (GPR 75) was recently identified as an effector for 20‐HETE, however, little is known about the sites where 20‐HETE is produced in the brain and where its receptors are located. In this study, we used immunohistochemistry (IHC) to identify neuroanatomical structures and landmarks that express CYP4A enzymes and the GPR 75 receptor in SS and control rats. We found that CYP4A enzymes are expressed in hippocampal and hypothalamic neurons, pial and penetrating arterioles in control rats. GPR 75 is expressed in the vascular smooth muscle cells of pial and penetrating arterioles and possibly pericytes at branch points of cerebral arterioles/capillaries. We also found that GPR 75 levels are higher and CYP4A levels are lower in SS vs. control by RT‐PCR, Western Blot and IHC. These findings are consistent with 20‐HETE's emerging role in the regulation of cerebral vascular diseases and dementia. Support or Funding Information This study was supported by grants DK104184 (Roman), HL138685 (Roman), AG050049 (Fan), P20GM104357 (Fan and Roman) from the National Institutes of Health, 16GRNT31200036 (Fan) from American Heart Association and the MD/Ph.D. program/Conway Scholarship (Gonzalez‐Fernandez). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .