Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats

The contributions of amiloride-sensitive and -insensitive fractions of alveolar fluid clearance in adult ventilated rats were studied under control conditions and after β-adrenergic stimulation. Rats were instilled with a 5% albumin solution containing terbutaline (10^-4 M) or dibutyryl-cGMP (DBcGMP; 10^-4 M) with or without the cyclic nucleotide-gated cation channel inhibitor l-cis-diltiazem (10^-3 M) and/or amiloride (10^-3 M). Alveolar fluid clearance over i h was 18 ± 2% in controls. In controls, amiloride inhibited 46 ± 15% of alveolar fluid clearance, whereas l-cis-diltiazem had no inhibitory effect. Terbutaline and DBcGMP stimulated alveolar fluid clearance by 85 ± 3 and 36 ± 5%, respectively. Amiloride and l-cis-diltiazem inhibited nearly equal fractions of terbutaline-stimulated alveolar fluid clearance when given alone. Amiloride and l-cis-diltiazem given together inhibited a significantly larger fraction of alveolar fluid clearance in terbutaline-stimulated rats and in DBcGMP-stimulated rats. Based on these data, terbutaline stimulation recruited both amiloride-sensitive and l-cis-diltiazem-sensitive pathways. In contrast, DBcGMP mainly recruited l-cis-diltiazem-sensitive pathways. Therefore, the amiloride-insensitive fraction of Na⁺-driven alveolar fluid clearance may be partly mediated through cyclic nucleotide-gated cation channels and activated by an increase in intracellular cGMP.