GABA receptors modulate ventilator‐induced lung injury

Mechanical ventilators are increasingly used in critical care units. However, they can cause lung injury including pulmonary edema. Our previous studies indicated that γ‐amino butyric acid receptors (GABAR) were involved in alveolar fluid homeostasis. The present study investigated the role of GABAR in ventilator‐induced lung injury. Adult female Sprague‐Dawley rats were subjected to high tidal volume ventilation (HVT) of 40 ml/kg body weight for 1 hour. HVT resulted in lung injury as indicated by increase in total protein in bronchoalveolar fluid, wet‐dry ratio (indication of pulmonary edema) and Evans Blue dye extravasation (indication of vascular damage). Intratracheal administration of GABA (500 μM) prior to ventilation significantly reduced the wet‐dry ratio. GABA‐mediated reduction was effectively blocked by GABA‐A receptor antagonist, bicuculline. The GABA‐mediated effect was not due to the vascular damage, since there were no changes in Evans Blue dye extravasation. However, the decrease in alveolar fluid clearance by HVT was partly prevented by GABA, which was blocked by bicuculline. These results suggest that GABA reduces HVT‐induced pulmonary edema via its effects on alveolar fluid clearance.