Losartan attenuates microvascular permeability in mechanical ventilator-induced lung injury in diabetic mice. 2014

Chang Chen, and Zongze Zhang, and Zijia Li, and Fan Zhang, and Mian Peng, and Yingying Chen, and Yanlin Wang
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Donghu Road, Wuhan, 430071, Hubei, People's Republic of China.

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.

UI MeSH Term Description Entries
D002199 Capillary Permeability The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement. Microvascular Permeability,Permeability, Capillary,Permeability, Microvascular,Vascular Permeability,Capillary Permeabilities,Microvascular Permeabilities,Permeabilities, Capillary,Permeabilities, Microvascular,Permeabilities, Vascular,Permeability, Vascular,Vascular Permeabilities
D003920 Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D000808 Angiotensinogen An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver in response to lowered blood pressure and secreted into blood circulation. Angiotensinogen is the inactive precursor of the ANGIOTENSINS produced in the body by successive enzyme cleavages. Cleavage of angiotensinogen by RENIN yields the decapeptide ANGIOTENSIN I. Further cleavage of angiotensin I (by ANGIOTENSIN CONVERTING ENZYME) yields the potent vasoconstrictor octapeptide ANGIOTENSIN II; and then, via other enzymes, other angiotensins also involved in the hemodynamic-regulating RENIN-ANGIOTENSIN SYSTEM. Hypertensinogen,Renin-Substrate,SERPINA8,Proangiotensin,Renin Substrate Tetradecapeptide,Serpin A8,Renin Substrate,Tetradecapeptide, Renin Substrate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016688 Mice, Inbred NOD A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked. Non-Obese Diabetic Mice,Mice, NOD,Mouse, Inbred NOD,Mouse, NOD,Non-Obese Diabetic Mouse,Nonobese Diabetic Mice,Nonobese Diabetic Mouse,Diabetic Mice, Non-Obese,Diabetic Mice, Nonobese,Diabetic Mouse, Non-Obese,Diabetic Mouse, Nonobese,Inbred NOD Mice,Inbred NOD Mouse,Mice, Non-Obese Diabetic,Mice, Nonobese Diabetic,Mouse, Non-Obese Diabetic,Mouse, Nonobese Diabetic,NOD Mice,NOD Mice, Inbred,NOD Mouse,NOD Mouse, Inbred,Non Obese Diabetic Mice,Non Obese Diabetic Mouse
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055397 Ventilator-Induced Lung Injury Lung damage that is caused by the adverse effects of PULMONARY VENTILATOR usage. The high frequency and tidal volumes produced by a mechanical ventilator can cause alveolar disruption and PULMONARY EDEMA. Lung Injury, Ventilator-Induced,Lung Injuries, Ventilator-Induced,Lung Injury, Ventilator Induced,Ventilator Induced Lung Injury,Ventilator-Induced Lung Injuries
D019808 Losartan An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II. 2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol,Cozaar,DuP-753,Losartan Monopotassium Salt,Losartan Potassium,MK-954,MK954,DuP 753,DuP753,MK 954,Monopotassium Salt, Losartan,Potassium, Losartan,Salt, Losartan Monopotassium

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