Blood plasma ATP elevations in response to hypoxia in mice require pannexin 1. NEW & NOTEWORTHY Export of vasodilator ATP from red blood cells requires pannexin 1. Panx1 channels participate in hemodynamic responses consistent with hypoxic vasodilation by regulating hypoxia-sensitive extracellular ATP levels in blood. Mean hypoxia-induced ATP export from RBCs from Panx1 −/− mice ( n = 8) was 82% lower than that from WT ( n = 8 P < 0.05). Mean venous plasma ATP during hypoxia was 57% lower in Panx1 −/− ( n = 6) vs. Estimation of hindlimb vascular conductance using data from the MAP and HBF experiments showed an average response of 28% for WT vs. WT ( n = 6) basally, and increased in WT but not Panx1 −/− mice during hypoxia (8 ± 6% vs. Hindlimb blood flow (HBF) was significantly lower in Panx1 −/− ( n = 6) vs. 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. Panx1 −/−erythrocytes (RBC) was determined ex vivo via tonometer experimentation across progressive deoxygenation.
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). We hypothesized that Panx1 channels and associated ATP export contribute to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to metabolic demand of tissue. Pannexin 1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo.
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