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Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin‐(1–7) or an angiotensin II receptor antagonist
Author(s) -
Wöstenvan Asperen Roelie M,
Lutter René,
Specht Patricia A,
Moll Gert N,
van Woensel Job B,
van der Loos Chris M,
van Goor Harry,
Kamilic Jelena,
Florquin Sandrine,
Bos Albert P
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2987
Subject(s) - ards , medicine , angiotensin ii , losartan , bronchoalveolar lavage , angiotensin converting enzyme 2 , angiotensin converting enzyme , angiotensin ii receptor type 1 , lung , angiotensin ii receptor antagonist , renin–angiotensin system , pharmacology , receptor , endocrinology , covid-19 , blood pressure , disease , infectious disease (medical specialty)
Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome. Angiotensin‐converting enzyme (ACE) and its effector peptide angiotensin (Ang) II have been implicated in the pathogenesis of ARDS. A counter‐regulatory enzyme of ACE, ie ACE2 that degrades Ang II to Ang‐(1–7), offers a promising novel treatment modality for this syndrome. As the involvement of ACE and ACE2 in ARDS is still unclear, this study investigated the role of these two enzymes in an animal model of ARDS. ARDS was induced in rats by intratracheal administration of LPS followed by mechanical ventilation. During ventilation, animals were treated with saline (placebo), losartan (Ang II receptor antagonist), or with a protease‐resistant, cyclic form of Ang‐(1–7) [cAng‐(1–7)]. In bronchoalveolar lavage fluid (BALF) of ventilated LPS‐exposed animals, ACE activity was enhanced, whereas ACE2 activity was reduced. This was matched by enhanced BALF levels of Ang II and reduced levels of Ang‐(1–7). Therapeutic intervention with cAng‐(1–7) attenuated the inflammatory mediator response, markedly decreased lung injury scores, and improved lung function, as evidenced by increased oxygenation. These data indicate that ARDS develops, in part, due to reduced pulmonary levels of Ang‐(1–7) and that repletion of this peptide halts the development of ARDS. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.