Losartan attenuates microvascular permeability in mechanical ventilator-induced lung injury in diabetic mice

Abstract

Mechanical ventilation can cause direct injury to the lungs, a type of injury known as ventilator-induced lung injury (VILI). VILI is associated with up-regulates angiotensinogen and AT1 receptor expression of in the lung. This work explored effects of losartan on VILI in diabetic mice. Ninty-six C57Bl/6 mice were randomly divided into six groups, control group (C group), diabetes group (D group), diabetes mechanical ventilation group (DV group), losartan control group (L+C group), losartan treatment group in diabetic mice (L+D group) and losartan treatment group in mechanical ventilation diabetic mice (L+DV group). Lung W/D, myeloperoxidase (MPO) activity, microvascular permeability, blood-gas analysis, Ang II concentrations and AT-1R protein expression were measured. Compared with D group, DV group increased Ang II concentrations, AT-1R protein expression, W/D ratio, MPO activity, and microvascular permeability. PaO2 were significantly lower in the DV group than D group or control group. Compared with DV group, L+DV group attenuates ventilator-induced lung injury in diabetic mice and prevented the increase Ang II concentrations, AT-1R protein expression and microvascular permeability caused by ventilation in diabetic mice. This study provides in vivo evidence that losartan attenuates microvascular permeability via down-regulates Ang II and AT-1R expression in mechanical ventilator-induced lung injury in diabetic mice.