The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by cyclic adenosine monophosphate.
The effect of subarachnoid hemorrhage on mechanisms of vasodilation mediated by cyclic adenosine monophosphate.
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DOI：
10.3171/jns.1998.89.1.0111
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发表时间：
1998-07
影响因子：
4.1
通讯作者：
Hisashi Onoue;Z. Katusic
中科院分区：
文献类型：
--
作者：
Hisashi Onoue;Z. Katusic
目的：本研究旨在确定蛛网膜下腔出血（SAH）是否影响负责对腺苷酸环化酶激活作出反应的犬脑动脉舒张的K+通道的功能。方法在正常犬和SAH犬（双出血模型）基底动脉环上观察K+通道抑制剂对腺苷酸环化酶直接激活剂forskolin舒张反应的影响。采用放射免疫分析法测定3 '，5'-环磷酸腺苷（cAMP）水平。在去除内皮的环中，由毛喉素诱导的舒张不受SAH的影响。Ca ~（++）激活的K ~+通道抑制剂Charybdotoxin（10 ~（-7）mol/L）可降低正常动脉和自体血注射动脉对Forskolin的舒张反应。这种抑制作用的charybdotoxin是显着更大的动脉参与SAH比正常血管。延迟整流钾通道抑制剂4-氨基吡啶（10（-3）mol/L）仅在SAH累及的动脉中降低对forskolin的舒张反应。与此相反，在正常和SAH动脉中，格列本脲（10（-5）mol/L）（一种腺苷5 '-三磷酸敏感性K+通道抑制剂）不影响对forskolin的舒张反应。毛喉素（3 × 10（-7）mol/L）使cAMP水平增加约10倍。在正常动脉和暴露于SAH的动脉中，用forskolin刺激后检测到的cAMP的基础值和增加的水平没有差异。结论SAH不影响cAMP的形成和腺苷酸环化酶的舒张反应。然而，在患病的动脉，K+通道承担更重要的作用，在介导的松弛反应，毛喉素，表明SAH可能会改变负责cAMP诱导的血管舒张的机制。
OBJECT This study was designed to determine whether subarachnoid hemorrhage (SAH) affects the function of the K+ channels responsible for relaxation of canine cerebral arteries in response to adenylate cyclase activation. METHOD The effect of K+ channel inhibitors on the arterial relaxation response to forskolin, a direct adenylate cyclase activator, was studied in rings of basilar arteries obtained from normal dogs and dogs in which SAH was induced (double-hemorrhage model). The levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured using the radioimmunoassay technique. In rings with the endothelium removed, relaxation induced by forskolin was not affected by SAH. The relaxation response to forskolin was reduced by charybdotoxin (10(-7) mol/L), a selective Ca++-activated K+ channel inhibitor, in normal arteries and arteries subjected to autologous blood injection. This inhibitory effect of charybdotoxin was significantly greater in arteries involved in SAH than in normal vessels. The relaxation response to forskolin was reduced by 4-aminopyridine (10(-3) mol/L), a delayed rectifier K+ channel inhibitor, only in arteries involved in SAH. In contrast, the relaxation response to forskolin was not affected by glyburide (10(-5) mol/L), an adenosine 5'-triphosphate-sensitive K+ channel inhibitor, in both normal and SAH arteries. Forskolin (3 x 10(-7) mol/L) produced an approximately 10-fold increase in levels of cAMP. The basal values and increased levels of cAMP detected after stimulation with forskolin were no different in normal arteries and those exposed to SAH. CONCLUSIONS These results demonstrate that formation of cAMP and the relaxation response to adenylate cyclase activation are not affected by SAH. However, in diseased arteries, K+ channels assume a more important role in the mediation of relaxation response to forskolin, indicating that SAH may change the mechanisms responsible for vasodilation induced by cAMP.