Miekisiak Greg, Kulik Tobias, Kusano Yoshikazu, Kung David, Chen Jiang-Fan, Winn H Richard
Department of Neurosurgery, Mount Sinai Medical School, New York, New York 10029, USA.
J Cereb Blood Flow Metab. 2008 Oct;28(10):1656-64. doi: 10.1038/jcbfm.2008.57. Epub 2008 Jun 11.
We evaluated cerebral blood flow by laser Doppler during 30 secs of hypoxia (0.10 FiO(2)) in anesthetized, ventilated adenosine 2a receptor knockout (A2aR KO) and wild-type (WT) mice to test the hypothesis that cerebral hypoxic hyperemia in KO mice would be attenuated. We also studied the effects of selective and nonselective A2aR antagonists. During 30 secs of hypoxia, P(a)O(2) decreased significantly (P<0.05) and to a similar degree in both types of mice, whereas P(a)CO(2) remained relatively stable. However, mean arterial blood pressure (MABP) decreased to a greater extent (P<0.05) during hypoxia in KO mice (58.6+/-1.5 mm Hg) than in WT animals (76.1+/-3.2 mm Hg). Consequently, in a separate group of mice, we stabilized and matched MABP during hypoxia. Hypoxic hyperemia was attenuated by 38% (P<0.05) in KO animals whose MABP was uncontrolled, and by 81% (P<0.05) in KO animals whose MABP changes were matched to the MABP in the hypoxic WT mice. In animals treated with adenosine antagonists, hypoxic hyperemia was decreased by 44% to 48% (P<0.05) in WT mice, but was without effect in KO mice. We conclude that adenosine via A2aR is responsible for a significant proportion of the hyperemia during hypoxia.
我们在麻醉、通气的腺苷 2a 受体敲除（A2aR KO）小鼠和野生型（WT）小鼠的 30 秒缺氧（0.10 FiO₂）期间，通过激光多普勒评估脑血流量，以检验 KO 小鼠脑缺氧性充血会减弱的假设。我们还研究了选择性和非选择性 A2aR 拮抗剂的作用。在 30 秒缺氧期间，两种类型小鼠的动脉血氧分压（P(a)O₂）均显著降低（P<0.05）且程度相似，而动脉血二氧化碳分压（P(a)CO₂）保持相对稳定。然而，KO 小鼠在缺氧期间平均动脉血压（MABP）下降幅度更大（P<0.05）（58.6±1.5 mmHg），高于野生型动物（76.1±3.2 mmHg）。因此，在另一组小鼠中，我们在缺氧期间稳定并匹配了 MABP。MABP 未得到控制的 KO 动物中，缺氧性充血减弱了 38%（P<0.05），而 MABP 变化与缺氧 WT 小鼠的 MABP 相匹配的 KO 动物中，缺氧性充血减弱了 81%（P<0.05）。在用腺苷拮抗剂治疗的动物中，WT 小鼠的缺氧性充血减少了 44%至 48%（P<0.05），但对 KO 小鼠没有影响。我们得出结论，通过 A2aR 的腺苷在很大程度上导致了缺氧期间的充血。
