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Angiotensin II receptor 1 blocker (losartan) restores the ability of the lung to clear edema in rats

Reem Ismael-Badarneh, Julia Guetta, Niroz Abu-Saleh, Geula Klorin, Gidon Berger, Zaid Abassi, Zaher Azzam
European Respiratory Journal 2013 42: P3921; DOI:
Reem Ismael-Badarneh
1The Ruth and Bruce Faculty of Medicine, Technion, Haifa, Israel
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Julia Guetta
2Internal Medicine B, Rambam: Human Health Care Campus, Haifa, Israel
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Niroz Abu-Saleh
1The Ruth and Bruce Faculty of Medicine, Technion, Haifa, Israel
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Geula Klorin
2Internal Medicine B, Rambam: Human Health Care Campus, Haifa, Israel
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Gidon Berger
2Internal Medicine B, Rambam: Human Health Care Campus, Haifa, Israel
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Zaid Abassi
1The Ruth and Bruce Faculty of Medicine, Technion, Haifa, Israel
2Internal Medicine B, Rambam: Human Health Care Campus, Haifa, Israel
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Zaher Azzam
1The Ruth and Bruce Faculty of Medicine, Technion, Haifa, Israel
2Internal Medicine B, Rambam: Human Health Care Campus, Haifa, Israel
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Abstract

Alveolar fluid clearance (AFC) is important in keeping the airspaces free of edema, mainly due to alveolar epithelial Na,K-ATPase pump and Na channels (ENaC). Angiotensin II (AngII) stimulates a variety of physiologic responses that supports arterial blood pressure and renal function. We previously showed that AngII impairs AFC (AFC in control rats was 0.44±0.04 ml/h (Mean ± SEM) and decreased by 40% in AngII treated rats (P = 0.003)). AngII effects are mediated by two specific receptors; AT1 and AT2. The localization of these two receptors in the lung was recently discovered, specifically in alveolar epithelial cells type II (ATII), but no studies investigated whether they play a role in AFC. In order to understand AngII mechanism, we investigated the effect of AT1 specific blocker (Losartan) using the isolated perfused lung model. Losartan administration, followed by AngII restored the inhibitory effect of AngII, indicating an AT1 mediated effect of AngII on AFC.

Furthermore, Oubain (Na,K-ATPase ihhibitor) and Amiloride (ENaC ihibitor) reduced AFC to 5.9±0.4 ml/hr and 5.8±0.11 ml/hr respectively. The administration of either Oubain or Amiloride with AngII tended to have more inhibitory effect on AFC (4.41±0.2 ml/hr or 5.29±0.08ml/hr respectively), suggesting that AngII signaling may target more than one protein. In ATII cells treated with AngII the expression of AT1 levels was upregulated. Notably, there was no significant change in αNa,K-ATPase and αENaC abundance after AngII treatment.

We herein provide a new mechanism of clinical relevance by which angiotensin adversely impairs the ability of the lungs to clear edema.

  • ALI (Acute Lung Injury)
  • Cell biology
  • Physiology
  • © 2013 ERS
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Angiotensin II receptor 1 blocker (losartan) restores the ability of the lung to clear edema in rats
Reem Ismael-Badarneh, Julia Guetta, Niroz Abu-Saleh, Geula Klorin, Gidon Berger, Zaid Abassi, Zaher Azzam
European Respiratory Journal Sep 2013, 42 (Suppl 57) P3921;

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Angiotensin II receptor 1 blocker (losartan) restores the ability of the lung to clear edema in rats
Reem Ismael-Badarneh, Julia Guetta, Niroz Abu-Saleh, Geula Klorin, Gidon Berger, Zaid Abassi, Zaher Azzam
European Respiratory Journal Sep 2013, 42 (Suppl 57) P3921;
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