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 beta-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 1 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.
Department of Animal Physiology, Lund University, S-223 62 Lund, Sweden.
A
A
Norlin
L N
LN
Lu
S E
SE
Guggino
M A
MA
Matthay
H G
HG
Folkesson
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001826:Body Fluids / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D013726:Terbutaline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D007473:Ion Channels; D014665:Vasodilator Agents; D003995:Dibutyryl Cyclic GMP; D000584:Amiloride; D000242:Cyclic AMP; D004110:Diltiazem; D006152:Cyclic GMP; D013726:Terbutaline