Impaired intracellular signal transduction via cyclic AMP contributes to cerebral vasospasm in rats with subarachnoid hemorrhage.
No drug can completely prevent vasospasm after subarachnoid hemorrhage. Impaired intracellular signal transduction by cyclic nucleotides might be involved. We investigated effects of intravenous isoproterenol and NKH477 on cerebral blood flow in rats with or without intracisternal injection of autologous blood one week previously. In controls without hemorrhage, isoproterenol at 0.01, 0.1, 1, and 10 mg kg(-1) min(-1) increased cerebral blood flow by 1.2%+/-9.5%, 19.7%+/-12.8%, 46.8%+/-23.5%, and 63.8%+/-32.9% respectively; 10mg kg(-1) min(-1) of isoproterenol increased systemic blood pressure by 66.6%+/-58.1%, while other doses decreased blood pressure. In the subarachnoid hemorrhage group, isoproterenol increased cerebral blood flow by -20.0%+/-6.5%, -7.6%+/-8.7%, 8.2%+/-8.8%, and 35.9%+/-83.1% respectively; 10 mg kg(-1) min(-1) of isoproterenol increased systemic blood pressure by 68.8%+/-79.5%, while other doses decreased blood pressure. In controls, NKH477 at 3, 10, and 30 mg kg(-1) increased cerebral blood flow by 2.3%+/-3.6%, 14.4%+/-7.0%, and 50.7%+/-14.6%, respectively; in the subarachnoid hemorrhage group, NKH477 changed cerebral blood flow by -1.3%+/-2.4%, 4.6%+/-2.8%, and -12.6%+/-10.8% (not significant difference from controls). NKH477 at 30 mg kg(-1) min(-1) decreased systemic blood pressure in both groups, but the effect in the hemorrhage group was greater. Either isoproterenol or NKH477 at appropriate doses can increase cerebral blood flow in vasospasm following subarachnoid hemorrhage without decreasing blood pressure.
Nakamizo
Akira
A
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Inamura
Takanori
T
Inoha
Satoshi
S
Amano
Toshiyuki
T
Ikezaki
Kiyonobu
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol