Nielsen, S., Terris, J., Andersen, D., Ecelbarger, C., Frøkiær, J., Jonassen, T., Marples, D., Knepper, M.A. and Peterson, J.S. (1997) Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct. Proceedings of the National Academy of Sciences, 94 (10). pp. 5450-5455. ISSN 0027-8424
We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 ± 3.4 vs. 4.1 ± 0.3 mmHg, and reduced plasma sodium concentrations (142.2 ± 1.6 vs. 149.1 ± 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 ± 53%, n=12) relative to sham-operated controls (100 ± 13%, n=14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective.Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 ± 28% of sham levels, n=6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF.
|Copyright, Publisher and Additional Information:||© Copyright 2001 National Academy of Sciences, U.S.A.|
|Institution:||The University of Leeds|
|Academic Units:||The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)|
|Depositing User:||Sherpa Assistant|
|Date Deposited:||14 Mar 2006|
|Last Modified:||16 Sep 2016 15:32|