Dysfunction of nitric oxide induces protein kinase C activation resulting in vasospasm after subarachnoid hemorrhage.
We hypothesize that the interaction between protein kinase C (PKC) and nitric oxide (NO) plays a role in the modulation of cerebral vascular tone, and the disturbance of this interaction following subarachnoid hemorrhage (SAH) results in vasospasm. To prove this hypothesis with direct evidence, PKC activities of smooth muscle cells of canine basilar arteries in the control and in the SAH groups were measured by an enzyme immunoassay method. N omega-nitro-L arginine (L-NA), an inhibitor of NO production, enhanced PKC activity. This enhancement was inhibited neither by 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) nor SIN-1, a NO releasing agent. PKC activity in the SAH was significantly higher than in the control; however, no further enhancement was produced with L-NA. In the SAH, PKC activity was not inhibited either by 8-bromo-cGMP or SIN-1. We conclude that NO maintains an appropriate vascular tone through inactivation of PKC, and that this effect is disturbed following SAH, resulting in PKC-dependent vascular contraction, such as vasospasm. On the other hand, once PKC has been activated, NO precursors do not inhibit PKC. These facts indicate NO inactivates PKC through the inhibition of phosphatidylinositol breakdown.
Nishizawa
S
S
Department of Neurosurgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Yamamoto
S
S
Yokoyama
T
T
Uemura
K
K
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007124:Immunoenzyme Techniques; D002546:Ischemic Attack, Transient / Q000209:etiology*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012016:Reference Values; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D006152:Cyclic GMP