Increased amiloride insensitive alveolar fluid clearance in rats with severe congestive heart failure

Abstract

Epithelial sodium channels (ENaC) play a central role in alveolar fluid clearance (AFC). We have previously shown that rats with severe congestive heart failure (CHF) have increased protein levels of the αENaC subunit, whereas the βENaC subunit is almost absent, suggesting predominance of the less efficient nonselective cation channel type in alveolar cells in severe CHF. The present study examined whether severe CHF was associated with quantitative changes in AFC. CHF was induced in male Wistar rats by LAD-ligation. Sham operated rats were used as controls. Rats were examined 3-5 weeks after LAD/Sham ligation. CHF had left ventricular end diastolic pressure > 15 mmHg and were postmortally devided into two groups based on right ventricular mass (RVM): Moderate CHF: RVM: 0.21±0.01g; Severe CHF: RVM: 0.37±0.04 g. RVM in Sham-operated controls: 0.16±0.01 g. AFC over 60 minutes was measured by installation of I125-Albumin in 5 % BSA in Ringer lactate into the lungs in ventilated anesthetized rats. The final to installed protein concentration ratio was significantly increased in severe CHF rats (1.27±0.03) and unchanged in moderate CHF rats (1.10±0.02) when compared to controls (1.10±0.01). AFC was completely inhibited with amiloride in both control rats (1.01±0.01) and rats with moderate CHF (1.01±0.05), but could not be inhibited in rats with severe CHF (1.24±0.06). The results indicate that rats with severe CHF have increased amiloride insensitive AFC, suggesting activation of alternative sodium transport pathways contributing to AFC in severe CHF. The study received financial support from the Danish Heart Foundation.