Chronological changes of arterial diameter, cGMP, and protein kinase C in the development of vasospasm.
Chronological changes of arterial diameter, cGMP, and protein kinase C in the development of vasospasm.
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DOI：
10.1161/01.str.26.10.1916
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发表时间：
1995-10
期刊：
影响因子：
8.3
通讯作者：
S. Nishizawa;S. Yamamoto;T. Yokoyama;H. Ryu;K. Uemura
中科院分区：
文献类型：
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作者：
S. Nishizawa;S. Yamamoto;T. Yokoyama;H. Ryu;K. Uemura
背景和目的我们假设一氧化氮对蛋白激酶C（PKC）的激活发挥负反馈控制作用，蛛网膜下腔出血后反馈控制的紊乱会导致PKC激活引起的血管痉挛。本研究旨在验证这一假设。方法不同的狗准备进行三个独立的实验：测量基底动脉的血管造影直径以及测定血管平滑肌细胞中的cGMP和PKC活性。在每个实验中，使用两种模型：轻度血管痉挛的单次出血模型和重度血管痉挛的两次出血模型。在这两个模型中，从第 1 天到第 7 天检查了这三个参数的时间变化。 结果 在单次出血模型中，第 4 天出现轻度血管痉挛和 cGMP 水平略有下降，然后在第 7 天均恢复到基线水平。 在整个研究期间，PKC 活性略有增强。在两次出血模型中，第5天观察到严重的血管痉挛和cGMP水平显着下降，并持续到第7天。PKC活性从第5天到第7天显着增强。两个模型在三个参数方面的差异具有统计学意义。结论 cGMP水平降低和PKC活性增强与严重血管痉挛的发生明显相关。我们得出的结论是，蛛网膜下腔出血扰乱了一氧化氮对 PKC 激活的反馈控制，导致 PKC 依赖性血管痉挛。
BACKGROUND AND PURPOSE We hypothesized that nitric oxide exerts a negative feedback control on protein kinase C (PKC) activation, and the disturbance of the feedback control after subarachnoid hemorrhage results in vasospasm due to PKC activation. This study was undertaken to verify this hypothesis. METHODS Different dogs were prepared for three separate experiments: measurement of the angiographic diameter of the basilar artery and determination of cGMP and PKC activity in vascular smooth muscle cells. In each experiment, two models were used: the single-hemorrhage model for mild vasospasm and the two-hemorrhage model for severe vasospasm. In both models, chronological changes of these three parameters were examined from day 1 until day 7. RESULTS In the single-hemorrhage model, mild vasospasm and a slight decrease of the cGMP level were noted on day 4, then both returned to the baseline levels on day 7. PKC activity was slightly enhanced throughout the study period. In the two-hemorrhage model, severe vasospasm and a significant decrease of the cGMP level were observed on day 5 and persisted until day 7. PKC activity was remarkably enhanced from day 5 until day 7. The differences between the two models with regard to the three parameters were statistically significant. CONCLUSIONS The decrease of cGMP level and the enhancement of PKC activity were obviously associated with the development of severe vasospasm. We conclude that subarachnoid hemorrhage disturbed the feedback control exerted by nitric oxide on PKC activation, leading to PKC-dependent vasospasm.