Pannexin1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contributes to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to tissue metabolic demand. Male and female mice devoid of Panx1 (Panx1-/-) and wild-type controls (WT) were anesthetized, mechanically ventilated, and instrumented with a carotid artery catheter or femoral artery flow transducer for hemodynamic and plasma ATP monitoring during inhalation of 21% (normoxia) or 10% oxygen (hypoxia). ATP export from WT vs. Panx1-/- erythrocytes (RBC) was determined ex vivo via tonometer experimentation across progressive deoxygenation. Mean arterial pressure (MAP) was similar in Panx1-/- (N=6) and WT (N=6) mice in normoxia, but the decrease in MAP in hypoxia seen in WT was attenuated in Panx1-/- mice (-16±9% vs -2±8%; P<0.05). Hindlimb blood flow (HBF) was significantly lower in Panx1-/- (N=6) vs. WT (N=6) basally, and increased in WT but not Panx1-/- mice during hypoxia (8±6% vs -10±13%; P<0.05). Estimation of hindlimb vascular conductance using data from the MAP and HBF experiments showed an average response of 28% for WT vs -9% for Panx1-/- mice. Mean venous plasma ATP during hypoxia was 57% lower in Panx1-/- (N=6) vs WT mice (N=6) (P<0.05). Mean hypoxia-induced ATP export from RBCs from Panx1-/- mice (N=8) was 82% lower than from WT (N=8) ( P<0.05). Panx1 channels participate in hemodynamic responses consistent with hypoxic vasodilation by regulating hypoxia-sensitive extracellular ATP levels in blood.

中文翻译：

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Pannexin 1 通道通过调节血液​​中 O2 敏感的细胞外 ATP 来控制对缺氧的血流动力学反应


Pannexin1 (Panx1) 通道输出 ATP，可能有助于体内缺氧期间血浆中血管舒张剂 ATP 浓度的增加。我们假设 Panx1 通道和相关的 ATP 输出有助于缺氧血管舒张，这是一种促进氧输送与组织代谢需求相匹配的机制。将缺乏 Panx1 (Panx1-/-) 和野生型对照 (WT) 的雄性和雌性小鼠麻醉、机械通气，并使用颈动脉导管或股动脉流量传感器进行仪器监测，以在吸入 21% 的过程中监测血流动力学和血浆 ATP （常氧）或 10% 氧气（缺氧）。 WT 与 Panx1-/- 红细胞 (RBC) 的 ATP 输出是通过渐进脱氧过程中的眼压计实验离体测定的。正常氧条件下 Panx1-/- (N=6) 和 WT (N=6) 小鼠的平均动脉压 (MAP) 相似，但 WT 中缺氧时 MAP 的降低在 Panx1-/- 小鼠 (-16 ±9% 与 -2±8%；P<0.05)。与 WT (N=6) 相比，Panx1-/- (N=6) 小鼠的后肢血流量 (HBF) 显着较低，并且在缺氧期间 WT 小鼠而非 Panx1-/- 小鼠的后肢血流量 (HBF) 有所增加（8±6% vs -10 ±13%；P<0.05)。使用来自 MAP 和 HBF 实验的数据对后肢血管电导的估计显示，WT 小鼠的平均响应为 28%，而 Panx1-/- 小鼠的平均响应为 -9%。 Panx1-/- (N=6) 缺氧期间的平均静脉血浆 ATP 比 WT 小鼠 (N=6) 低 57% (P<0.05)。 Panx1-/- 小鼠 (N=8) 的红细胞缺氧诱导的平均 ATP 输出比 WT (N=8) 低 82% ( P<0.05)。 Panx1 通道通过调节血液​​中缺氧敏感的细胞外 ATP 水平参与与缺氧血管舒张一致的血流动力学反应。