Contribution of amiloride-insensitive pathways to alveolar fluid clearancein adult rats

The contributions of amiloride-sensitive and -insensitive fractions of alve olar fluid clearance in adult ventilated rats were studied under control co nditions and after beta -adrenergic stimulation. Rats were instilled with a 5% albumin solution containing terbutaline (10(-4) M) or dibutyryl-cGMP (D BcGMP; 10-4 M) with or without the cyclic nucleotide-gated cation channel i nhibitor l-cis-diltiazem (10(-3) M) and/or amiloride (10-3 M). Alveolar flu id clearance over 1 h was 18 +/- 2% in controls. In controls, amiloride inh ibited 46 +/- 15% of alveolar fluid clearance, whereas l-cis-diltiazem had no inhibitory effect. Terbutaline and DBcGMP stimulated alveolar fluid clea rance by 85 +/- 3 and 36 +/- 5%, respectively. Amiloride and l-cis-diltiaze m inhibited nearly equal fractions of terbutaline-stimulated alveolar fluid clearance when given alone. Amiloride and l-cis-diltiazem given together i nhibited a significantly larger fraction of alveolar fluid clearance in ter butaline-stimulated rats and in DBcGMP-stimulated rats. Based on these data , tertbutaline stimulation recruited both amiloride-sensitive and E-cis-dil tiazem-sensitive pathways. In contrast, DBcGMP mainly recruited l-cis-dilti azem-sensitive pathways. Therefore, the amiloride-insensitive fraction of N at-driven alveolar fluid clearance may be partly mediated through cyclic nu cleotide-gated cation channels and activated by an increase in intracellula r cGMP.