VAChT reduction increased mortality probably due to alveolar edema in a model of lung injury induced by intestinal isquemia/reperfusion in female mice

Abstract

Introduction: ARDS induced by iIR injury is a relevant clinical condition characterized lung inflammation and non-cardiodiogenic edema. Acetylcholine (ACh) release is dependent on the levels of vesicular acetylcholine transporter (VAChT) and is the mediator of cholinergic anti-inflammatory system. Aims: To evaluate the effect of VAChT reduction in lung injury induced by iIR injury. Methods: Female VAChT KDHOM (70% reduction of VAChT and ACh release) and littermate (WT) mice were submitted to iIR by obstruction of superior mesenteric artery (45min) followed by 2h of reperfusion. Vascular permeability and recruitment of inflammatory cells into lung were investigated. A VAChT KDHOM group received PNU, an agonist of nAChR-α7, before iIR procedure. Results: 43% of VAChT KDHOM mice died in the reperfusion period compared to 5.2% of WT mice. iIR induced an increased lung vascular permeability (204.5±21.7µg/mg of lung dry weight) in VAChT KDHOM compared to WT+iIR (113.8±13.8µg/mg of lung dry weight) and to naive mice (WT: 117.9±11.8 and VAChT KDHOM: 97.5±11.0µg/mg of lung dry weight) (P Conclusion: Reduced levels of VAChT induce mortality in female mice after iIR due to pulmonary edema. nAChR-α7 exerts a protective effect on lung, reinforcing the cholinergic anti-inflammatory pathway influence in this model.