Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling.
Neuronal activity evokes localized changes in blood flow. Although this response, termed neurovascular coupling, is widely used to monitor human brain function and diagnose pathology, the cellular mechanisms that mediate the response remain unclear. We investigated the contribution of glial cells to neurovascular coupling in the acutely isolated mammalian retina. We found that light stimulation and glial cell stimulation can both evoke dilation or constriction of arterioles. Light-evoked and glial-evoked vasodilations were blocked by inhibitors of cytochrome P450 epoxygenase, the synthetic enzyme for epoxyeicosatrienoic acids. Vasoconstrictions, in contrast, were blocked by an inhibitor of omega-hydroxylase, which synthesizes 20-hydroxyeicosatetraenoic acid. Nitric oxide influenced whether vasodilations or vasoconstrictions were produced in response to light and glial stimulation. Light-evoked vasoactivity was blocked when neuron-to-glia signaling was interrupted by a purinergic antagonist. These results indicate that glial cells contribute to neurovascular coupling and suggest that regulation of blood flow may involve both vasodilating and vasoconstricting components.
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Monica R
MR
Metea
Eric A
EA
Newman
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology / Q000502:physiology / Q000528:radiation effects; D020013:Calcium Signaling / Q000528:radiation effects; D002208:Caproates / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A / Q000037:antagonists & inhibitors / Q000502:physiology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009457:Neuroglia / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D010782:Photolysis; D011335:Proadifen / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D020318:Rats, Long-Evans; D012171:Retinal Vessels / Q000187:drug effects / Q000201:enzymology / Q000502:physiology* / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
C121755:6-(2-propargyloxyphenyl)hexanoic acid; D000578:Amidines; D002208:Caproates; D003497:Cyclic N-Oxides; D065607:Cytochrome P-450 Enzyme Inhibitors; D005136:Eye Proteins; C000708209:HET0016; D006834:Hydrazines; D006893:Hydroxyeicosatetraenoic Acids; D007093:Imidazoles; D020030:Nitric Oxide Donors; C112653:PAPA NONOate; D058914:Purinergic Antagonists; C061868:inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D008825:Miconazole; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D019001:Nitric Oxide Synthase; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A; D015126:8,11,14-Eicosatrienoic Acid; D019331:NG-Nitroarginine Methyl Ester