Obligatory Roles of Protein Kinase C and Nitric Oxide in the Regulation of Cerebral Vascular Tone: An Implication of a Pathogenesis of Vasospasm After Subarachnoid Haemorrhage
Obligatory Roles of Protein Kinase C and Nitric Oxide in the Regulation of Cerebral Vascular Tone: An Implication of a Pathogenesis of Vasospasm After Subarachnoid Haemorrhage
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蛋白激酶 C 和一氧化氮在脑血管张力调节中的必然作用：蛛网膜下腔出血后血管痉挛发病机制的暗示
DOI：
10.1007/s007010050215
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发表时间：
1998
影响因子：
2.4
通讯作者：
K. Uemura
中科院分区：
文献类型：
--
作者：
S. Nishizawa;N. Yokota;T. Yokoyama;K. Uemura
我们以前表明，犬基底动脉表现出紧张和有力的，蛋白激酶C（PKC）依赖性收缩时，一氧化氮（NO）被抑制。我们还报道了在犬蛛网膜下腔出血模型中，血管痉挛的血管造影严重程度、增强的PKC和减弱的鸟苷酸、13′，15 ′-环磷酸（cGMP）活性的时间变化之间的线性相关性。cGMP的活性是NO功能的指标。基于这些证据，我们假设PKC和NO调节脑血管张力。我们特别关注NO在维持血管张力的PKC活性负反馈机制中的作用。为了进一步证实我们的假设，我们研究了PKC下调对NO抑制引起的血管紧张性收缩的影响。血管平滑肌细胞中PKC活性的显著下调是通过与10− 5 mole/L的佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）孵育24小时获得的。紧张性和有效的收缩诱导的NO-抑制完全抑制在PKC下调的动脉，即使动脉表现出显着的收缩在高K+的解决方案。这些结果表明，一个强制性的作用，PKC活性在紧张性收缩时，NO被抑制，并支持我们以前的数据。一氧化氮通过抑制PKC活性诱导血管舒张。蛛网膜下腔出血损害这种抑制作用，导致PKC依赖性血管收缩，如血管痉挛。
We previously showed that a canine basilar artery manifested tonic and potent, protein kinase C (PKC)-dependent contractions when nitric oxide (NO) was inhibited. We also reported a linear correlation between chronological changes in the angiographic severity of vasospasm, enhanced PKC, and attenuated guanosine, 13′,15′-cyclic monophosphate (cGMP) activity in a canine subarachnoid haemorrhage model. The activity of cGMP is an indicator of NO-function. Based on this evidence, we have hypothesized that PKC and NO regulate cerebral vascular tone. We particularly focused on the role of NO in a negative feedback mechanism on PKC activity in the maintenance of vascular tone. To further confirm our hypothesis, we investigated the effect of PKC down-regulation on the tonic vascular contraction induced by NO-inhibition.Canine basilar artery was used in the experiment. Significant down-regulation of PKC activity in vascular smooth muscle cells was obtained by incubation with 10−5mole/L of phorbol 12-myristate 13-acetate (PMA) for 24 hours. The tonic and potent contraction induced by NO-inhibition was completely suppressed in the PKC down-regulated artery, even though the artery manifested a significant contraction in high-K+solutions. These results indicate an obligatory role of PKC activity in tonic contraction when NO is inhibited, and support our previous data. Nitric oxide induces vascular relaxation by inhibiting PKC activity. Subarachnoid haemorrhage impairs this inhibition, resulting in PKC-dependent vascular contraction, such as vasospasm.