title: Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.
abstract: We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH.
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan. Electronic address: tmurata@shinshu-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Dietrich
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Tetsuyoshi
authors.initials: T
authors.lastname: Horiuchi
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hongo
authors.affiliation: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Dacey
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002413:Cations, Divalent; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005110:Extracellular Space / Q000737:chemistry; D017616:Magnesium Compounds / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002413:Cations, Divalent; D017616:Magnesium Compounds; D026902:Potassium Channel Blockers; D015221:Potassium Channels
keywords: Cerebral penetrating arterioles; Delayed cerebral vasospasm; Magnesium; Potassium channels; Subarachnoid hemorrhage