High-dose methylprednisolone prevents vasospasm after subarachnoid hemorrhage through inhibition of protein kinase C activation.
We have previously shown that the inflammatory process after subarachnoid hemorrhage causes vasospasm. The efficacy of methylprednisolone by suppression of the inflammatory process has been reported, although pharmacological mechanisms have not been clarified. The purpose of this study was to investigate the pharmacological mechanism of methylprednisolone on vasospasm. Using the 'two-hemorrhage' canine model, progression of angiographic vasospasm was assessed in nontreated and treated groups with methylprednisolone. Methylprednisolone 10 mg kg-1 was injected i.v. after the first injection of blood, and the same dose was injected every 12 h until day 7. Protein kinase C (PKC) activity of canine basilar arteries in both groups was measured during the course of vasospasm. In the isometric tension study, the effect of methylprednisolone on tensions induced by phorbol 12-myristate 13-acetate (PMA), or high-K+ solution, was also evaluated. Methylprednisolone significantly reduced severity of vasospasm. In the treated group, PKC activity was not enhanced compared with the nontreated group at any point. Methylprednisolone inhibited tonic tension induced by PMA, but not that induced by high-K+ solution. We conclude that methylprednisolone prevents severity of vasospasm through inhibition of PKC activation, but does not work as a Ca2+ channel blocker.
Chen
Duo
D
Department of Neurosurgery, Hamamatsu University School of Medicine, 3600 Handacho, Hamamatsu, Shizuoka 431-3192, Japan.
Nishizawa
Shigeru
S
Yokota
Naoki
N
Ohta
Seiji
S
Yokoyama
Tetsuo
T
Namba
Hiroki
H
D000792:Angiography; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D001488:Basilar Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008775:Methylprednisolone / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology
D000893:Anti-Inflammatory Agents; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D008775:Methylprednisolone