Park Ik-Seong, Meno Joseph R, Witt Cordelie E, Chowdhary Abhineet, Nguyen Thien-Son, Winn H Richard, Ngai Al C, Britz Gavin W
Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Neurosurg. 2009 Nov;111(5):1008-13. doi: 10.3171/2009.3.JNS096.
Cerebrovascular dysfunction after subarachnoid hemorrhage (SAH) may contribute to ischemia, but little is known about the contribution of intracerebral arterioles. In this study, the authors tested the hypothesis that SAH inhibits the vascular reactivity of intracerebral arterioles and documented the time course of this dysfunction.
Subarachnoid hemorrhage was induced using an endovascular filament model in halothane-anesthetized male Sprague-Dawley rats. Penetrating intracerebral arterioles were harvested 2, 4, 7, or 14 days postinsult, cannulated using a micropipette system that allowed luminal perfusion and control of luminal pressure, and evaluated for reactivity to vasodilator agents.
Spontaneous tone developed in all pressurized (60 mm Hg) intracerebral arterioles harvested in this study (from 66 rats), with similar results in the sham and SAH groups. Subarachnoid hemorrhage did not affect dilation responses to acidic pH (6.8) but led to a persistent impairment of endothelium-dependent dilation responses to adenosine triphosphate (p < 0.01), as well as a transient attenuation (p < 0.05) of vascular smooth muscle-dependent dilation responses to adenosine, sodium nitroprusside, and 8-Br-cyclic guanosine monophosphate (cGMP). Impairment of NO-mediated dilation was more sustained than adenosine- and 8-Br-cGMP-induced responses (up to 7 days postinsult compared with 2 days). All smooth muscle-dependent responses returned to sham levels by 14 days after SAH.
Subarachnoid hemorrhage led to a persistent impairment of endothelium-dependent dilation and a transient attenuation of vascular smooth muscle-dependent dilation responses to adenosine. Impairment of NO-mediated dilation occurred when the response to cGMP was intact, suggesting a change in cGMP levels rather than an alteration in intracellular mechanisms downstream from cGMP.
蛛网膜下腔出血（SAH）后的脑血管功能障碍可能导致缺血，但关于脑内小动脉的作用知之甚少。在本研究中，作者检验了SAH抑制脑内小动脉血管反应性的假说，并记录了这种功能障碍的时间进程。
在氟烷麻醉的雄性Sprague-Dawley大鼠中，使用血管内丝线模型诱导蛛网膜下腔出血。在损伤后2、4、7或14天收获穿透性脑内小动脉，使用允许管腔灌注和管腔压力控制的微量移液器系统插管，并评估对血管扩张剂的反应性。
在本研究中收获的所有加压（60mmHg）脑内小动脉（来自66只大鼠）均出现自发张力，假手术组和SAH组结果相似。蛛网膜下腔出血不影响对酸性pH值（6.8）的扩张反应，但导致对三磷酸腺苷的内皮依赖性扩张反应持续受损（p<0.01），以及对腺苷、硝普钠和8-溴环磷酸鸟苷（cGMP）的血管平滑肌依赖性扩张反应短暂减弱（p<0.05）。与腺苷和8-溴环磷酸鸟苷诱导的反应相比，一氧化氮介导的扩张受损更持久（损伤后7天与2天相比）。所有平滑肌依赖性反应在SAH后14天恢复到假手术水平。
蛛网膜下腔出血导致内皮依赖性扩张持续受损，以及对腺苷的血管平滑肌依赖性扩张反应短暂减弱。当对cGMP的反应完整时，一氧化氮介导的扩张受损，提示cGMP水平改变而非cGMP下游细胞内机制改变。
