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 a ssociated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQ P2), in the renal collecting duct, CHF was induced by left coronary ar tery ligation, Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pres sures (LVEDP): 26.9 +/- 3.4 vs, 4.1 +/- 0.3 mmHg, and reduced plasma s odium concentrations (142.2 +/- 1.6 vs, 149.1 +/- 1.1 mEq/liter). Quan titative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 +/- 5 3%, n = 12) relative to sham-operated controls (100 +/- 13%, n = 14), In contrast, immunoblotting demonstrated a lack of an increase in expr ession of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective, Furthermore, postinfarction animals with out LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 +/- 28% of sham levels, n = 6), Immunocytochemistry an d immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellula r vesicles in collecting duct cells from rats with severe CHF, consist ent with enhanced trafficking of AQP2 to the apical plasma membrane, T he selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retentio n and hyponatremia in severe CHF.