title: The Role of Angiotensin II and Cyclic AMP in Alveolar Active Sodium Transport.
abstract: Active alveolar fluid clearance is important in keeping airspaces free of edema. Angiotensin II plays a role in the pathogenesis of hypertension, heart failure and others. However, little is known about its contribution to alveolar fluid clearance. Angiotensin II effects are mediated by two specific receptors; AT1 and AT2. The localization of these two receptors in the lung, specifically in alveolar epithelial cells type II, was recently reported. We hypothesize that Angiotensin II may have a role in the regulation of alveolar fluid clearance. We investigated the effect of Angiotensin II on alveolar fluid clearance in rats using the isolated perfused lung model and isolated rat alveolar epithelial cells. The rate of alveolar fluid clearance in control rats was 8.6% ± 0.1 clearance of the initial volume and decreased by 22.5%, 28.6%, 41.6%, 48.7% and 39% in rats treated with 10-10 M, 10-9 M, 10-8 M, 10-7 M or 10-6 M of Ang II respectively (P < 0.003). The inhibitory effect of Angiotensin II was restored in losartan, an AT1 specific antagonist, pretreated rats, indicating an AT1 mediated effect of Ang II on alveolar fluid clearance. The expression of Na,K-ATPase proteins and cAMP levels in alveolar epithelial cells were down-regulated following the administration of Angiotensin II; suggesting that cAMP may be involved in AngII-induced reduced Na,K-ATPase expression, though the contribution of additional factors could not be excluded. We herein suggest a novel mechanism of clinical relevance by which angiotensin adversely impairs the ability of the lungs to clear edema.
authors.affiliation: Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Reem
authors.initials: R
authors.lastname: Ismael-Badarneh
authors.affiliation: Internal Medicine "B", Rambam: Human Health Care Campus, Haifa, Israel.
authors.forename: Julia
authors.initials: J
authors.lastname: Guetta
authors.affiliation: Internal Medicine "B", Rambam: Human Health Care Campus, Haifa, Israel.
authors.forename: Geula
authors.initials: G
authors.lastname: Klorin
authors.affiliation: Internal Medicine "B", Rambam: Human Health Care Campus, Haifa, Israel; Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Gidon
authors.initials: G
authors.lastname: Berger
authors.affiliation: Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Niroz
authors.initials: N
authors.lastname: Abu-Saleh
authors.affiliation: Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
authors.affiliation: Internal Medicine "B", Rambam: Human Health Care Campus, Haifa, Israel; Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel; The Rappaport Family Institute for Research in the Medical Sciences, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Zaher S
authors.initials: ZS
authors.lastname: Azzam
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D017136:Ion Transport; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D000804:Angiotensin II; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase