ACE mediates ventilator-induced lung injury in rats via angiotensin II but not bradykinin

¹ paediatric Intensive Care Dept, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands
² Depts of Pulmonology and Experimental Immunology, Academic Medical Center
³ Dept of Anesthesiology, Erasmus-MC Faculty, Rotterdam; and Dept of Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
⁴ Center for paediatric Clinical Epidemiology, Academic Medical Center
⁵ Dept of Pathology, Academic Medical Center
⁶ Dept of Anesthesiology, Erasmus-MC Faculty, Rotterdam

^* To whom correspondence should be addressed. E-mail: r.m.vanasperen{at}amc.uva.nl.

	Abstract

Ventilator-induced lung injury (VILI) is characterized by inflammation and apoptosis, but underlying mechanisms are poorly understood. A role for angiotensin-converting enzyme (ACE) via angiotensin II (Ang II) and/or bradykinin in acute lung injury was proposed. We assessed whether ACE and, if so, Ang II and/or bradykinin are implicated in inflammation and apoptosis by mechanical ventilation.

Rats were ventilated for 4 h with low or high pressure amplitudes in the absence or presence of the ACE inhibitor captopril. Non-ventilated animals served as controls. ACE activity, Ang II and bradykinin, as well as inflammatory parameters (total protein, macrophage inflammatory protein-2 and Interleukin-6) were determined. Apoptosis was assessed by the number of activated caspase-3 and TUNEL positive cells.

BALF ACE activity, levels of total protein, inflammatory parameters and the number of apoptotic cells were increased in the high pressure amplitudes group as compared to the control group. Blocking ACE activity by captopril attenuated inflammation and apoptosis in this latter group. Similar results were obtained by blocking Ang II receptors, but blocking bradykinin receptors did not attenuate the anti-inflammatory and anti-apoptotic effects of captopril.

We conclude that inflammation and apoptosis in VILI is, at least in part, due to ACE-mediated Ang II production.