Relation between protein kinase C and calmodulin systems in cerebrovascular contraction: investigation of the pathogenesis of vasospasm after subarachnoid hemorrhage.
The protein kinase C (PKC) and calmodulin systems each play a role in vascular contraction. However, the correlation of these two systems in producing contraction has been unclear. To clarify the pathophysiology of vasospasm after subarachnoid hemorrhage, the authors demonstrated tonic contraction of the cerebral artery in a study of isometric tension, and investigated the correlation of the PKC and calmodulin systems in producing the contraction. To develop better management for vasospasm, they also examined the effect of calmodulin antagonists on tonic contraction. The development of isometric tension in canine basilar arteries was measured, with the following results: 1) tonic contraction was dependent on the PKC system, but initiation of the contraction by the calmodulin system was necessary for the subsequent PKC-dependent tonic contraction; 2) specific calmodulin antagonists like chlorpromazine and pimozide partially inhibited the tonic contraction associated with PKC activation; 3) another calmodulin antagonist, trifluoperazine, inhibited the PKC system as well. On the basis of these results, the authors conclude that the PKC system plays a role in the development of vasospasm. In the early phase of contraction, the calmodulin system contributes to the subsequent fully-activated, PKC-induced tonic contraction. To manage vasospasm, a specific calmodulin antagonist would therefore not be sufficient. Suppression of both the calmodulin and PKC systems with trifluoperazine in the earliest stage of vasospasm is recommended.
Nishizawa
S
S
Department of Neurosurgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Peterson
J W
JW
Shimoyama
I
I
Uemura
K
K
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D001921:Brain / Q000098:blood supply*; D002147:Calmodulin / Q000502:physiology*; D002746:Chlorpromazine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014268:Trifluoperazine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D002147:Calmodulin; D010868:Pimozide; D014268:Trifluoperazine; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D011188:Potassium; D002746:Chlorpromazine