title: Downregulation of aquaporin-1 in alveolar microvessels in lungs adapted to chronic heart failure.
abstract: The threshold pressure for lung edema formation is increased in severe chronic heart failure (CHF) due to reduced microvascular permeability. The water channel aquaporin-1 (AQP1) is present in the pulmonary microvascular endothelium, and a number of studies suggest the importance of AQP1 as a molecular determinant of pulmonary microvascular water transport. The present study examined the abundance and localization of AQP1 in lungs from rats with CHF. We used two different models of CHF: ligation of the left anterior descending coronary artery (LAD ligation) and aorta-banding (AB). Sham-operated rats served as controls. Echocardiographic verification of left ventricular dysfunction, enhanced left ventricular end-diastolic pressure, and right ventricular hypertrophy confirmed the presence of CHF. Western blotting of whole-lung homogenates revealed significant downregulation of AQP1 in LAD-ligated rats (24 h: 58 ± 5% of sham; 3 weeks: 8 ± 3% of sham; 9 weeks: 16 ± 6% of sham) and after AB (30 weeks: 37 ± 5% of sham), whereas the protein levels of the specific endothelial cell marker PECAM-1 was increased 3 weeks after LAD ligation (229 ± 20% of sham), but unchanged after 9 weeks and in the AB rats compared to controls. Immunohistochemical examination 3 weeks after LAD ligation showed intact labeling of PECAM-1 but an almost complete absence of AQP1 in the pulmonary alveolar microvessels in the CHF rats. These results suggest that downregulation of AQP1 in the alveolar microvessels may act as a compensatory mechanism to protect against formation of excessive pulmonary edema in CHF.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Panum build 18.5, 2200 Copenhagen N, Denmark. kat.mikala@gmail.com
authors.forename: Katrine M
authors.initials: KM
authors.lastname: Müllertz
authors.forename: Claes
authors.initials: C
authors.lastname: Strøm
authors.forename: Simon
authors.initials: S
authors.lastname: Trautner
authors.forename: Ole
authors.initials: O
authors.lastname: Amtorp
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Sten
authors.initials: S
authors.lastname: Christensen
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.forename: Thomas E N
authors.initials: TE
authors.lastname: Jonassen
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D051398:Aquaporin 1 / Q000378:metabolism*; D002908:Chronic Disease; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D008026:Ligation; D008297:Male; D055806:Microvessels / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply*; D011654:Pulmonary Edema / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051398:Aquaporin 1