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Pannexin1 channel‐mediated ATP release and the vasodepressor response to hypoxia (1079.19)
Author(s) -
Kirby Brett,
Petkov Brian,
Zhu Hongmei,
McMahon Timothy
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1079.19
Subject(s) - hypoxia (environmental) , vasodilation , extracellular , medicine , chemistry , endocrinology , anesthesia , oxygen , biochemistry , organic chemistry
Plasma ATP is hypothesized to mediate hypoxic vasodilation, and pannexin1 (panx1) channels present in red blood cells (RBCs) and vascular tissue transport ATP in response to hypoxia. We tested the hypothesis that intravascular panx1 channel‐mediated ATP release is obligatory to hypoxia‐induced hypotension in anesthetized mice. Functional loss of panx1‐mediated ATP release to hypoxia was observed in isolated RBCs from mice devoid of panx1 (KO; panx1‐/‐) vs wild‐type controls (WT). Mice were anesthetized with isoflurane, mechanically ventilated, and mean arterial pressure (MAP) was measured via carotid artery catheter during inhalation of 21 and 10% O2. MAP was similar for KO and WT in normoxia, but hypoxia‐induced hypotension was abolished in Panx1‐/‐ vs WT mice (Δ ‐1±3 vs ‐14±3 mmHg). Heart rate during hypoxia did not fall, consistent with hypoxia‐induced peripheral vasodilation. Venous plasma ATP during hypoxia was lower in Panx1‐/‐ vs WT mice (67±6 vs 166±23 nM). These data demonstrate a key role for panx1 channels in governing blood extracellular ATP and the vasodepressor response to hypoxia, consistent with their proposed roles in hypoxic vasodilation. Grant Funding Source : Supported by NIH HL113943