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。犬基底动脉血管条在器官培养中反复暴露于或不暴露于氧合血红蛋白3天（氧合血红蛋白处理条和对照条）。高水平钾（80mM）和尿苷5'-三磷酸（310^<-4>M）引起的收缩在oxyhb处理组以浓度依赖性方式减少。一氧化氮和8-溴环鸟苷单磷酸（8-溴- cgmp）引起的松弛不受影响。当细胞外钙浓度（[Ca^<++>] _e）从外液浓度10^<-8> M改变为10^<-3> M时，肌原性张力发生。在[Ca^<++>] _e = 10^<-5> M和10^<-4> M时，oxyhb处理组的肌原性张力（以各节段最大收缩的百分比表示）增强。两组之间动脉壁的被动顺应性无显著差异。这些结果表明，长时间暴露于体外氧合血红蛋白会导致收缩能力下降和对[Ca^<++>] _6的敏感性增加，这与先前在痉挛动脉中的发现一致。相比之下，8-溴- cgmp介导的松弛途径的损伤和动脉壁僵硬的增加，这些已经报道发生在痉挛动脉中，并不是由长时间暴露于体外的OxyHb诱导的。

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.