Selective effects of subarachnoid hemorrhage on cerebral vascular responses to 4-aminopyridine in rats
Selective effects of subarachnoid hemorrhage on cerebral vascular responses to 4-aminopyridine in rats
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DOI：
10.1161/01.str.31.10.2460
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发表时间：
2000-10-01
期刊：
影响因子：
8.3
通讯作者：
Sobey, CG
中科院分区：
文献类型：
--
作者：
Quan, L;Sobey, CG
背景和目的--我们推测蛛网膜下腔出血(SAH)后脑血管功能的某些异常可能涉及K(+)通道功能的潜在改变。因此，我们使用药物抑制剂，观察SAH对两种K(+)通道在体内调节基底动脉内径和体外膜电位(E(M))的影响。两天后，通过颅窗准备检查血管活性药物对基底动脉的影响。比较对照组和SAH大鼠对4-氨基吡啶(4-AP)、3-氨基吡啶(3-AP)、四乙基铵(TEA)、5-羟色胺、乙酰胆碱和腺苷的血管反应。进一步的细胞内微电极研究评估了4-AP和5-羟色胺对对照组和SAH大鼠基底动脉E(M)的影响。结果：对照组和SAH大鼠的基线动脉直径分别为236±5微米和220±7微米(P<；0.05)。4-AP使对照组大鼠基底动脉收缩，SAH大鼠对4-AP的反应减弱。SAH对茶或5-羟色胺的收缩反应无影响。SAH大鼠对乙酰胆碱的血管扩张反应受损，而对腺苷的反应没有不同。对照组静息E(M)为-81±-3 mV，SAH组静息E(M)为-79±-3 mV。4-AP和5-羟色胺对基底动脉均有去极化作用，但4-AP对SAH动脉的去极化作用不明显。结论4-AP通过抑制电压依赖性K(+)通道，在体内通过平滑肌去极化引起脑血管收缩。此外，SAH后基底动脉K(+)通道的功能可能选择性降低，从而导致脑血管功能障碍。
Background and Purpose-We postulated that some abnormalities in cerebrovascular function after subarachnoid hemorrhage (SAH) may involve underlying alterations in K(+) channel function. Thus, using pharmacological inhibitors, we assessed the influence of SAH on function of 2 types of K(+) channel in regulation of basilar artery diameter in vivo and membrane potential (E(m)) in vitro.Methods-Rats were injected with saline (control) or autologous blood (SAH) into the cisterna magna. Two days later, effects of vasoactive drugs on the basilar artery were examined with a cranial window preparation. Vascular responses to 4-aminopyridine (4-AP), 3-aminopyridine (3-AP), tetraethylammonium (TEA), serotonin, acetylcholine, and adenosine were compared in control and SAH rats. Additional studies using intracellular microelectrodes evaluated the effects of 4-AP and serotonin on E(m) of basilar arteries isolated from control and SAH rats.Results-Baseline artery diameter was 236+/-5 mu m in control rats and 220+/-7 mu m in SAH rats (P < 0.05). 4-AP, but not 3-AP, constricted the basilar artery in control rats, and responses to 4-AP were reduced in SAH rats. Constrictor responses to TEA or serotonin were unaffected by SAH. Vasodilator responses to acetylcholine were impaired in SAH rats, whereas responses to adenosine were not different. Resting E(m) was -81+/-3 mV in control arteries and -79+/-3 mV in SAH arteries. Both 4-AP and serotonin depolarized the basilar artery, but only 4-AP-induced depolarization was impaired in SAH arteries.Conclusions These data suggest that 4-AP induces cerebral vasoconstriction in vivo through smooth muscle depolarization due to inhibition of voltage-dependent K(+) channels. Furthermore, function of these K(+) channels may be selectively reduced in the basilar artery after SAH and thus could contribute to cerebral vascular dysfunction.