Sun H, Kanamaru K, Ito M, Suzuki H, Kojima T, Waga S, Kureishi Y, Nakano T
Department of Neurosurgery, Mie University School of Medicine, Mie, Japan.
Stroke. 1998 Oct;29(10):2149-54. doi: 10.1161/01.str.29.10.2149.
Subarachnoid hemorrhage (SAH) impairs both contraction and relaxation response in cerebral arteries. We tested the hypothesis that cerebral vasospasm might be ATP-independent contraction, such as latch state, and protein synthesis might be substantially downregulated due to ATP consumption after long-lasting contraction.
Chronic cerebral vasospasm was induced in the canine 2-hemorrhage model of SAH. The normal and spastic basilar arteries were stabilized in Krebs-Henseleit solution, and contraction was induced by 30 micromol/L prostaglandin F2alpha (PGF2alpha) in vitro and in vivo. Before and at 15 minutes and 1 hour after the treatment with PGF2alpha, the levels of phosphorylated 20-kDa myosin light chain (MLC20) were measured. The time course of expression of contraction proteins actin and MLC20, and contraction-inhibiting proteins h-caldesmon and calponin was determined by immunoblotting techniques.
A significant vasospasm occurred in the basilar artery during days 4 to 21, most prominently on days 7 and 14. There were no significant differences in the baseline levels of phosphorylated MLC20 between normal and spastic basilar arteries. The increase in MLC20 phosphorylation by PGF2alpha was significantly attenuated in the spastic basilar artery in vitro and in vivo (P<0.05). The immunoreactivity for actin, h-caldesmon, and calponin in the spastic basilar arteries was progressively decreased until day 14 and returned to the normal level on day 21. In contrast, protein levels of MLC20 did not significantly change during days 0 to 21.
Chronic cerebral vasospasm closely resembles the latch state, and temporary deficiencies of contractile proteins may result from increased destruction and inhibition of protein synthesis.
蛛网膜下腔出血（SAH）会损害脑动脉的收缩和舒张反应。我们检验了这样一种假设，即脑血管痉挛可能是三磷酸腺苷（ATP）非依赖性收缩，如强直状态，并且由于长时间收缩后ATP消耗，蛋白质合成可能会大幅下调。
在犬类SAH的双次出血模型中诱导慢性脑血管痉挛。将正常和痉挛的基底动脉置于Krebs-Henseleit溶液中使其稳定，在体外和体内用30微摩尔/升前列腺素F2α（PGF2α）诱导收缩。在用PGF2α治疗前以及治疗后15分钟和1小时，测量磷酸化20-kDa肌球蛋白轻链（MLC20）的水平。通过免疫印迹技术确定收缩蛋白肌动蛋白和MLC20以及收缩抑制蛋白h-钙调蛋白和钙调磷酸蛋白表达的时间进程。
在第4至21天基底动脉出现显著的血管痉挛，在第7天和第14天最为明显。正常和痉挛的基底动脉之间磷酸化MLC20的基线水平没有显著差异。在体外和体内，PGF2α引起的MLC20磷酸化增加在痉挛的基底动脉中显著减弱（P<0.05）。痉挛的基底动脉中肌动蛋白、h-钙调蛋白和钙调磷酸蛋白的免疫反应性在第14天之前逐渐降低，并在第21天恢复到正常水平。相比之下，在第0至21天MLC20的蛋白质水平没有显著变化。
慢性脑血管痉挛与强直状态非常相似，收缩蛋白的暂时缺乏可能是由于蛋白质合成的破坏增加和抑制所致。
