Interrelation between protein kinase C and nitric oxide in the development of vasospasm after subarachnoid hemorrhage.
This study was undertaken to investigate how protein kinase C (PKC) and nitric oxide (NO) interact to regulate the vascular tone, and how their interaction contributes to the development of vasospasm after subarachnoid hemorrhage (SAH). For these purposes, vasospasm was conducted with a canine model. We investigated the following subjects with arteries from intact animals and those from the SAH model, and compared the results between the two; tension at rest of isometric tension study, the effect of PKC inhibitors and of an inhibitor of NO synthesis on the tension at rest, and levels of guanosine 3',5'-cyclic monophosphate (cGMP) as an indicator of NO production. The tension at rest was enhanced in the artery from the SAH model compared to that from intact animals, and it was PKC-dependent. Arteries from intact animals but not those from the SAH model developed tonic tensions by NO inhibitors, and these tonic tensions were suppressed by PKC inhibitors, and also by cGMP. An enzyme immunoassay revealed a decreased cGMP level in the SAH model. The evidence indicates that NO exerts a negative feedback control on PKC activation. Subarachnoid hemorrhage interferes with this feedback control, resulting in PKC-dependent enhanced vascular tone and vasospasm.
Nishizawa
S
S
Department of Neurosurgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Yamamoto
S
S
Uemura
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*
D000470:Alkaloids; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010879:Piperazines; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D006152:Cyclic GMP; D019311:Staurosporine