Description:
Introduction: The P2X7 receptor is an unusual non‐desensitizing, cation selective, ion channel directly gated by extracellular ATP or ATP analogs. It is involved in several processes relevant to inflammation and immunity. Oxidized ATP (oATP) is a potent irreversible antagonist of P2X7 receptor, and it is not influenced by the presence of extracellular Na+ or K+. In our previous vascular functional study, we found that high concentration of oATP inhibits contractile response to PE.Hypothesis: oATP induces a factor to abolish the contractile response of PE in mouse aortic rings.Methods & Results: Vascular reactivity was evaluated using standard methods in aortic rings, with endothelium, from male C57Bl/6 mice. Incubation with oATP (24 h) inhibited 10−6M PE‐induced contractions in a concentration‐dependent way: oATP 50 μM (80.37±3.37 %, normalized to 120 mM KCl), 100 μM (47.11±1.54 %), 150 μM (46.43±4.64 %), and 250 μM (32.77±4.37 %). L‐NAME or 1400W reversed the abolished PE contractile response in 250 μM oATP. However, indomethacin did not. oATP did not alter eNOS, iNOS, or nNOS protein expression, but decreased COX2 protein expression.Conclusion: oATP abolished PE‐induced contractile response in mouse aortic rings. This effect might be induced by activation of the nitric oxide signaling pathway.