Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct.
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.
Nielsen
S
S
Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark. SN@ANA.AAU.DK
Terris
J
J
Andersen
D
D
Ecelbarger
C
C
Frokiaer
J
J
Jonassen
T
T
Marples
D
D
Knepper
M A
MA
Petersen
J S
JS
D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001794:Blood Pressure; D015870:Gene Expression; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007473:Ion Channels / Q000096:biosynthesis*; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012964:Sodium / Q000097:blood; D016277:Ventricular Function, Left
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D007473:Ion Channels; D012964:Sodium