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A novel role for P450 eicosanoids in the neurogenic control of cerebral blood flow
Author(s) -
Iliff Jeffrey John,
Close Liesl N.,
Selden Nathan R.,
Alkayed Nabil J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a871-a
Subject(s) - cerebral blood flow , medicine , neuroscience , pharmacology , psychology
The P450 eicosanoids epoxyeicostrienoic acids (EETs) are endogenous regulators of cerebral blood flow that are synthesized by P450 epoxygenases and metabolized by soluble epoxide hydrolase (sEH). EETs dilate cerebral blood vessels and protect against cerebral ischemia. Pharmacological inhibition and genetic deletion of sEH to increase endogenous EETs are protective against ischemic brain injury, however, the distribution of sEH in brain vasculature is unknown. Immunoblot analysis of isolated cerebral microvessels and immunohistochemistry of thin brain slices suggested that sEH is expressed in parenchymal vascular cells. Unexpectedly, immunofluorescent analysis of middle cerebral and basilar arteries revealed vivid sEH immunoreactivity (IR) in extrinsic perivascular nerves. Immunoflourescent double‐labeling revealed that sEH‐IR predominantly co‐localized with neuronal nitric oxide synthase (nNOS) and vasoactive intestinal peptide (VIP), two markers for parasympathetic vasodilator nerve fibers. We further detected expression of EETs‐synthetic enzyme P450 2C11 in nitrergic parasympathetic nerve fibers. The presence of enzymes involved in EETs production and inactivation within extrinsic vasodilator fibers suggests a novel role for EETs in neurogenic control of cerebral arteries.