Thromboxane A2 synthetase inhibitor failed to ameliorate the arterial narrowing during the chronic phase of cerebral vasospasm.
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.
Toshima
Y
Y
Laboratory for Pharmacology, Asahi Chemical Industry, Tagata-Gun, Japan.
Satoh
S
S
Ikegaki
I
I
Asano
T
T
Suzuki
Y
Y
Shibuya
M
M
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*
D004791:Enzyme Inhibitors; D008689:Methacrylates; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013930:Thromboxane-A Synthase; C034364:ozagrel; C049347:fasudil