Mechanisms regulating cerebral blood flow as therapeutic targets.
Regulation of cerebral blood flow (CBF) is critical for the maintenance of neural function and hence survival of the organism. Since the brain does not store glycogen, unlike muscle, a constant supply of glucose and oxygen are needed for the minute-by-minute demands of cerebral function. This review focuses on important lipid mediators that act as reciprocal regulators of cerebral artery diameter and their potential as targets for therapeutic intervention in diseases such as ischemia, stroke and subarachnoid hemorrhage. Cytochrome P450 metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) provides a mechanism for the constriction and relaxation of cerebral arteries, respectively. Additionally, EETs have mitogenic potential and may contribute to angiogenesis in the brain, which has important implications during recovery from cerebral injury. Finally, we discuss novel inhibitors of 20-HETE formation and actions as well as interventions to enhance EET production in cerebrovascular disease.
Pratt
Phillip F
PF
Cardiovascular Center, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. ppratt@mcw.edu
Medhora
Meetha
M
Harder
David R
DR
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000502:physiology; D002536:Cerebral Arteries / Q000201:enzymology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans
D003577:Cytochrome P-450 Enzyme System