Kajita Y, Dietrich H H, Dacey R G
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, USA.
J Neurosurg. 1996 Nov;85(5):908-16. doi: 10.3171/jns.1996.85.5.0908.
After subarachnoid hemorrhage (SAH), cerebral arteries display impaired vasomotor control, resulting in decreased regional cerebral blood flow. Recently, propagation of vasomotor responses has been recognized as an important regulatory mechanism in microcirculation. In this study, the authors tested the hypothesis that oxyhemoglobin (OxyHb) inhibits the vasodilatory effect of chemical mediators such as adenosine and adenine nucleotides at a local and/or propagated site. Penetrating intracerebral arterioles were surgically isolated from the middle cerebral arteries of rat brains, cannulated, and observed videomicroscopically in an organ bath under an inverted microscope. The effects of 10(-5) M OxyHb on vasoactive responses to adenosine, adenosine diphosphate (ADP), and adenosine triphosphate (ATP) were examined. The drugs were extraluminally applied either to the bath (10(-10)-10(-3) M) or, using pressure microejection (pipette concentration 10(-2) M), locally. The ATP and ADP initially constricted and then significantly dilated the vessels after both extraluminal application and microapplication. Furthermore, local microstimulation by these drugs produced conducted vasodilation. Adenosine elicited significant vasodilation after both extraluminal and local stimulation. Again, conducted vasodilation was observed. The vasomotor responses that were induced by a maximum local stimulation corresponded in magnitude to those observed at bath concentrations of 10(-5) to 10(-4) M of the same drug. Pretreatment with OxyHb constricted arterioles to an average of 87% of control and blunted extraluminally induced dilation at low concentrations (10(-10)-10(-8)) of ATP and ADP, but did not affect vasodilation induced by 10(-4) M or greater concentrations of ATP, ADP, or adenosine. Although the local response to local microstimulation was unaltered, propagated vasodilation as a response to ATP, ADP, and adenosine was significantly attenuated by OxyHb. These findings indicate that vasodilatory propagation plays an important role in the regulation of brain microcirculation and that its impairment by OxyHb could, in part, explain the cerebral hypoperfusion that is observed after SAH.
蛛网膜下腔出血（SAH）后，脑动脉的血管舒缩控制受损，导致局部脑血流量减少。最近，血管舒缩反应的传播已被认为是微循环中的一种重要调节机制。在本研究中，作者检验了以下假设：氧合血红蛋白（OxyHb）在局部和/或传播部位抑制化学介质如腺苷和腺嘌呤核苷酸的血管舒张作用。从大鼠脑的大脑中动脉手术分离出穿透性脑内小动脉，插管，并在倒置显微镜下的器官浴中进行视频显微镜观察。研究了10⁻⁵ M OxyHb对腺苷、二磷酸腺苷（ADP）和三磷酸腺苷（ATP）血管活性反应的影响。药物通过管腔外施加于浴槽（10⁻¹⁰ - 10⁻³ M），或使用压力微注射（移液器浓度10⁻² M）进行局部施加。在管腔外施加和微注射后，ATP和ADP最初使血管收缩，然后显著扩张血管。此外，这些药物的局部微刺激产生传导性血管舒张。腺苷在管腔外和局部刺激后均引起显著的血管舒张。同样，观察到传导性血管舒张。最大局部刺激诱导的血管舒缩反应在幅度上与在浴槽中10⁻⁵至10⁻⁴ M相同药物浓度下观察到的反应相当。用OxyHb预处理使小动脉收缩至平均对照值的87%，并减弱了低浓度（10⁻¹⁰ - 10⁻⁸）ATP和ADP管腔外诱导的扩张，但不影响10⁻⁴ M或更高浓度的ATP、ADP或腺苷诱导的血管舒张。尽管对局部微刺激的局部反应未改变，但OxyHb显著减弱了对ATP、ADP和腺苷反应的传导性血管舒张。这些发现表明，血管舒张传播在脑微循环调节中起重要作用，并且OxyHb对其的损害可能部分解释了SAH后观察到的脑灌注不足。
