Epoxyeicosatrienoic acid-dependent cerebral vasodilation evoked by metabotropic glutamate receptor activation in vivo. Am J Physiol Heart Circ Physiol 2011 Aug;301(2):H373-81
Date
05/24/2011Pubmed ID
21602473Pubmed Central ID
PMC3154671DOI
10.1152/ajpheart.00745.2010Scopus ID
2-s2.0-79961046351 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Group I metabotropic glutamate receptors (mGluR) on astrocytes have been shown to participate in cerebral vasodilation to neuronal activation in brain slices. Pharmacological stimulation of mGluR in brain slices can produce arteriolar constriction or dilation depending on the initial degree of vascular tone. Here, we examined whether pharmacological stimulation of mGluR in vivo increases cerebral blood flow. A 1-mM solution of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) superfused at 5 μl/min over the cortical surface of anesthetized rats produced a 30 ± 2% (±SE) increase in blood flow measured by laser-Doppler flowmetry after 15-20 min. The response was completely blocked by superfusion of group I mGluR antagonists and attenuated by superfusion of an epoxyeicosatrienoic acid (EET) antagonist (5 ± 4%), an EET synthesis inhibitor (11 ± 3%), and a cyclooxygenase-2 inhibitor (15 ± 3%). The peak blood flow response was not significantly affected by administration of inhibitors of cyclooxygenase-1, neuronal nitric oxide synthase, heme oxygenase, adenosine A(2B) receptors, or an inhibitor of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE). The blood flow response gradually waned following 30-60 min of DHPG superfusion. This loss of the flow response was attenuated by a 20-HETE synthesis inhibitor and was prevented by superfusion of an inhibitor of epoxide hydrolase, which hydrolyzes EETs. These results indicate that pharmacological stimulation of mGluR in vivo increases cerebral blood flow and that the response depends on the release of EETs and a metabolite of cyclooxygenase-2. Epoxide hydrolase activity and 20-HETE synthesis limit the duration of the response to prolonged mGluR activation.
Author List
Liu X, Li C, Gebremedhin D, Hwang SH, Hammock BD, Falck JR, Roman RJ, Harder DR, Koehler RCMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAdenosine A2 Receptor Antagonists
Analysis of Variance
Animals
Arterioles
Blood Flow Velocity
Cerebral Arteries
Cerebral Cortex
Cerebrovascular Circulation
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Epoxide Hydrolases
Excitatory Amino Acid Agonists
Excitatory Amino Acid Antagonists
Glycine
Heme Oxygenase (Decyclizing)
Hydroxyeicosatetraenoic Acids
Laser-Doppler Flowmetry
Male
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Rats
Rats, Wistar
Receptor, Adenosine A2B
Receptors, Metabotropic Glutamate
Regional Blood Flow
Resorcinols
Signal Transduction
Time Factors
Vasodilation
Vasodilator Agents
