Possible mechanism to induce protein kinase C-dependent arterial smooth muscle contraction after subarachnoid haemorrhage

• Published in: Acta neurochirurgica 1995-01, Vol.137 (3-4), p.217-225
• Main Authors: Ohta, S, Nishihara, J, Oka, Y, Todo, H, Kumon, Y, Sakaki, S
• Format: Article
• Language: English
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Basilar Artery - physiopathology; Diglycerides - metabolism; Dogs; Female; Hydroxyeicosatetraenoic Acids - metabolism; Ischemic Attack, Transient - physiopathology; Lipid Peroxidation - physiology; Male; Muscle, Smooth, Vascular - physiopathology; Protein Kinase C - physiology; Subarachnoid Hemorrhage - physiopathology; Vasoconstriction - physiology
• ISSN: 0001-6268; 0942-0940
• DOI: 10.1007/BF02187196

A possible mechanism for the induction of protein kinase C (PKC)-dependent vascular contraction independent to the increase of intracellular Ca++ was investigated in the pathogenesis of cerebral vasospasm in the double subarachnoid haemorrhage (SAH) model. The level of 1,2-diacylglycerol (DAG), which is an intrinsic PKC activator, significantly increased from days 4 to 7 in the basilar artery after the initial SAH, and the continuous administration of 1,2-bis(nicotinamido)-propane (AVS), a novel free radical scavenger, not only lowered the concentration of lipid peroxides in the CSF but also successfully suppressed the basilar arterial wall in the same model. It was suggested that lipid peroxides generated in the subarachnoid clot affect the DAG content of the cerebral artery. Analysis of hydroxy-eicosatetraenoic acids (HETEs) with high performance liquid chromatography (HPLC) revealed the production of relatively large amount of 12-HETE in the subarachnoid clot. To examine the potential effect of exogenous 12-HETE on the DAG content of the cerebral artery, the basilar artery was incubated with 12-HETE in vitro. 12-HETE induced a concentration-dependent slow increase in DAG content in the arterial wall after 6 hours of incubation. Under conditions in which DAG formation was facilitated by the Ca(++)-ionophore, DAG accumulation in the basilar artery was enhanced in the presence of 12-HETE. It was suggested that 12-HETE generated in the subarachnoid clot, induced DAG accumulation in the arterial wall by inhibition of DAG metabolism, resulting in the induction of prolonged PKC-dependent smooth muscle contraction in the pathogenesis of cerebral vasospasm.