title: Thromboxane A2 synthetase inhibitor failed to ameliorate the arterial narrowing during the chronic phase of cerebral vasospasm.
abstract: To determine the pathogenetic mechanism underlying the maintenance of arterial narrowing during the chronic phase of cerebral vasospasm caused by subarachnoid hemorrhage (SAH), we examined the effect of ozagrel, a thromboxane A2 (TXA2) synthetase inhibitor, on chronic vasospasm in a canine two-hemorrhage model in comparison with that of fasudil, an inhibitor of protein kinases. The magnitude of the vasospasm was determined angiographically. On SAH day 7, a vasospasm was observed in every dog. Intraarterial or intravenous administration of ozagrel (3 mg/kg/30 min) did not reverse the vasospasm but tended to increase bleeding. In contrast, intraarterial administration of fasudil (3 mg/kg/30 min) significantly reversed the vasospasm. These findings suggest that: 1) TXA2 does not participate in the maintenance of chronic vasospasm after SAH; and 2) the protein kinases, particularly myosin-light chain kinase and protein kinase C, are involved in the pathogenesis of arterial narrowing during the chronic phase of cerebral vasospasm.
authors.affiliation: Laboratory for Pharmacology, Asahi Chemical Industry, Tagata-Gun, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Toshima
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.forename: I
authors.initials: I
authors.lastname: Ikegaki
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002543:Cerebral Hemorrhage / Q000188:drug therapy; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D008689:Methacrylates; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013930:Thromboxane-A Synthase; C034364:ozagrel; C049347:fasudil