LPS induces permeability injury in lung microvascular endothelium via AT(1) receptor.
Lipopolysaccharide (LPS) is known to stimulate the circulation and local production of angiotensin II (Ang II). To assess whether Ang II plays a role in LPS-induced acute lung injury, rats were injected with LPS, the microvascular endothelial permeability injury was evaluated by histological changes, increased pulmonary wet/dry weight ratio, and pulmonary microvascular protein leak. Besides, increased rat pulmonary microvascular endothelial cell monolayer permeability coefficient (K(f)) was measured after treatment with LPS and/or Ang II, respectively. LPS/Ang II, treatment resulted in a significant increase in K(f). Ang II cooperates with LPS to further increase K(f). Hence, LPS increases pulmonary microvascular endothelial permeability both in vitro and in vivo. Local lung Ang II was increased in response to LPS challenge, and elevated Ang II ulteriorly exacerbates LPS-induced endothelium injury. [Sar(1),Ile(8)]Ang II, a selective block of Ang II type 1 (AT(1)) receptors, eliminated these changes significantly. Our conclusion is that the LPS-induced lung injury may be mediated by the AT(1) receptor.
Zhang
Hong
H
Department of Geriatric Medicine, The First Affiliated Hospital of Anhui Medical University, Anhui, Hefei 230022, China. ZhangHong38@ahmu,edu.cn
Sun
Geng-Yun
GY
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology*; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
D008070:Lipopolysaccharides; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II