Angiotensin-converting enzyme (ACE) mediates the ventilator-induced inflammatory response in healthy lungs via angiotensin II (Ang II). A rat model was used to examine the role of ACE and Ang II in the inflammatory response during mechanical ventilation of preinjured (ie, lipopolysaccharide [LPS]-exposed) lungs. When indicated, rats were pretreated with the ACE inhibitor captopril and/or intratracheal administration of LPS. The animals were ventilated for 4 hours with moderate pressure amplitudes. Nonventilated animals served as controls. ACE activity and levels of Ang II and inflammatory mediators (interleukin-6, Cytokine-induced Neutrophil Chemoattractant (CINC)-3, interleukin-1β, and interleukin-10) were determined in bronchoalveolar lavage fluid (BALF). The localization of ACE and Ang II type 1 receptor in lung tissue was determined by immunohistochemistry. The role of the Ang II pathway was assessed by using its receptor antagonist Losartan. Mechanical ventilation of LPS-exposed animals increased ACE activity and levels of inflammatory mediators in BALF compared with ventilated nonexposed and LPS-exposed nonventilated animals. Blocking ACE by captopril attenuated the lung inflammatory response. Furthermore, increased ACE activity in BALF was accompanied by increased levels of Ang II and enhanced expression of its receptor on alveolar cells. Blocking the Ang II receptor attenuated the inflammatory mediator response to a larger extent than by blocking ACE. In conclusion, during mechanical ventilation ACE, via Ang II, mediates the inflammatory response of both healthy and preinjured lungs. Copyright

dx.doi.org/10.2353/ajpath.2010.090565, hdl.handle.net/1765/63168
American Journal of Pathology
Department of Anesthesiology

Wösten-van Asperen, R.M, Lutter, R, Specht, P, van Woensel, J.B, van der Loos, C.M, Florquin, S, … Bos, A.P. (2010). Ventilator-induced inflammatory response in lipopolysaccharide-exposed rat lung is mediated by angiotensin-converting enzyme. American Journal of Pathology, 176(5), 2219–2227. doi:10.2353/ajpath.2010.090565