title: Carbon monoxide mediates vasodilator effects of glutamate in isolated pressurized cerebral arterioles of newborn pigs.
abstract: The excitatory neurotransmitter glutamate causes dilation of newborn pig cerebral arterioles in vivo that is blocked by inhibition of carbon monoxide (CO) production. CO, a potent dilator in cerebral circulation in vivo, is produced endogenously in cerebral microvessels via heme oxygenase (HO). In isolated pressurized cerebral arterioles (approximately 200 microm) from newborn pigs, we investigated the involvement of CO and the endothelium in response to glutamate. A CO-releasing molecule, dimanganese decacarbonyl (10(-8)-10(-6) M), dilated cerebral arterioles. Glutamate (10(-6)-10(-4) M) and 1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD; 10(-6)-10(-5) M), a N-methyl-D-aspartate (NMDA) receptor agonist, caused cerebral vascular dilation. Dilation of cerebral arterioles to glutamate and cis-ACPD was abolished by chromium mesoporphyrin (CrMP; 10(-6) M), a HO inhibitor. In contrast, CrMP did not alter dilation to isoproterenol, a -adrenergic receptor agonist. Endothelium-denuded cerebral arterioles did not dilate to glutamate or bradykinin (endothelium-dependent dilator), whereas responses to isoproterenol were preserved. These data indicate that cerebral arterioles from newborn pigs may directly respond to glutamate and the NMDA receptor agonists by endothelium-dependent dilation that involves stimulation of CO production via the HO pathway in the endothelium.
authors.affiliation: Department of Physiology, Vascular Biology Center, University of Tennessee Health Sciences Center, Memphis, 38163, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fiumana
authors.forename: Helena
authors.initials: H
authors.lastname: Parfenova
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Jaggar
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D002248:Carbon Monoxide / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis; D008652:Mesoporphyrins / Q000494:pharmacology; D011312:Pressure; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008652:Mesoporphyrins; D016194:Receptors, N-Methyl-D-Aspartate; C427471:chromium mesoporphyrin; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)