title: 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.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Donghu Road, Wuhan, 430071, Hubei, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.forename: Zongze
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zijia
authors.initials: Z
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Mian
authors.initials: M
authors.lastname: Peng
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000808:Angiotensinogen; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology; D019808:Losartan / Q000008:administration & dosage*; D051379:Mice; D016688:Mice, Inbred NOD; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000808:Angiotensinogen; D019808:Losartan