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 of the United States of America - Tập 94 Số 10 - Trang 5450-5455 - 1997
Søren Nielsen1, J Terris1, Ditte Andersen1, Carolyn Ecelbarger1, Jørgen Frøkiær1, Thomas E. N. Jonassen1, David Marples1, Mark A. Knepper1, Jørgen S. Petersen1
1Department of Cell Biology, Institute of Anatomy, and Institute of Experimental Clinical Research, University of Aarhus, DK-8000 Aarhus C, Denmark; Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; Department of Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; and Department of Physiology, University of Leeds, Leeds LSZ 9NQ, United Kingdom

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 94 Số 10

5450-5455

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