Pathogenesis of Cerebral Vasospasm ; Evaluation of Ca^<2+> sensitivity of contractile proteins.

本研究旨在确定氧合血红蛋白（OxyHb）是否与蛛网膜下腔出血后慢性血管痉挛期间观察到的脑动脉功能改变有关。犬基底动脉的血管条在器官培养物中保持3天，有或没有重复暴露于OxyHb（OxyHb处理和对照条）。在OxyHb处理组中，由高水平钾（80 mM）和尿苷5 '-三磷酸（310 μ M）引起的收缩<-4>以浓度依赖性方式减少。一氧化氮和8-溴-环磷酸鸟苷（8-bromo-cGMP）引起的舒张反应不受影响。在OxyHb处理的环中，由钙通道阻断剂地尔硫卓引起的舒张减弱。当细胞外钙浓度（[Ca^++] _e）从10 μ M改变<-8>到10 μ <-3>M时，产生肌源性张力。在[Ca^&lt;++&gt;] _e为10 μ M和10 μ M时，OxyHb治疗组的肌源性张力（表示为每个节段最大收缩的百分比）增加<-5><-4>。两组之间动脉壁的被动顺应性没有显着差异。这些结果表明，长时间暴露于氧合血红蛋白（OxyHb）可使离体血管收缩能力降低，对[Ca^++] _6的敏感性增加，这与以往在痉挛性动脉中的发现一致。相比之下，8-溴-cGMP-介导的松弛途径的损伤和动脉壁的增加的刚度，这已被报道发生在痉挛的动脉中，并没有通过长时间暴露于OxyHb在体外诱导。

The present study was undertaken to determine whether oxyhemoglobin (OxyHb) is responsible for the functional alterations in the cerebral arteries observed during chronic vasospasm after subarachnoid hemorrhage. Vascular strips of canine basilar arteries were kept in organ culture for 3 days with or without repetitive exposure to OxyHb (OxyHb-treated and control strips). Contractions elicited by high levels of potassium (80mM) and uridine 5'-triphosphate (310^<-4>M) were reduced in the OxyHb-treated group in a concentration-dependent manner. The relaxations evoked by nitric oxide and 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) were not affected. Relaxations elicited by the calcium channel blocker, diltiazem, were attenuated in the OxyHb-treated rings, When the extracellular calcium concentration ([Ca^<++>] _e) was changed from a concentration in the external solution of 10^<-8> M to 10^<-3> M,myogenic tension developed. Myogenic tension, expressed as a percentage of the maximum contraction in each segment, was augmented in the OxyHb-treated group at [Ca^<++>] _e of 10^<-5> M and 10^<-4> M.There were no significant differences in passive compliance of the arterial wall between the two groups. These results demonstrated that prolonged exposure to OxyHb in vitro results in a decrease in contractile capacity and an increase in sensitivity to [Ca^<++>] _6, in agreement with previous findings in spastic arteries. By contrast, impairment of the 8-bromo-cGMP-mediated relaxation pathway and increased stiffnes of the arterial wall, which have been reported to occur in spastic arteries, were not induced by prolonged exposure to OxyHb in vitro.