Norlin A, Lu L N, Guggino S E, Matthay M A, Folkesson H G
Department of Animal Physiology, Lund University, S-223 62 Lund, Sweden.
J Appl Physiol (1985). 2001 Apr;90(4):1489-96. doi: 10.1152/jappl.2001.90.4.1489.
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.
在对照条件下以及β-肾上腺素能刺激后，研究了成年通气大鼠肺泡液体清除中对阿米洛利敏感和不敏感部分的作用。给大鼠气管内滴注含特布他林（10⁻⁴ M）或二丁酰环磷鸟苷（DBcGMP；10⁻⁴ M）的5%白蛋白溶液，同时或不添加环核苷酸门控阳离子通道抑制剂l-顺式地尔硫䓬（10⁻³ M）和/或阿米洛利（10⁻³ M）。对照组1小时的肺泡液体清除率为18±2%。在对照组中，阿米洛利抑制了46±15%的肺泡液体清除率，而l-顺式地尔硫䓬没有抑制作用。特布他林和DBcGMP分别使肺泡液体清除率提高了85±3%和36±5%。单独给予时，阿米洛利和l-顺式地尔硫䓬抑制特布他林刺激的肺泡液体清除率的比例几乎相等。同时给予阿米洛利和l-顺式地尔硫䓬时，在特布他林刺激的大鼠和DBcGMP刺激的大鼠中，抑制肺泡液体清除率的比例显著更大。基于这些数据，特布他林刺激募集了对阿米洛利敏感和对l-顺式地尔硫䓬敏感的两条途径。相比之下，DBcGMP主要募集对l-顺式地尔硫䓬敏感的途径。因此，Na⁺驱动的肺泡液体清除中对阿米洛利不敏感的部分可能部分通过环核苷酸门控阳离子通道介导，并由细胞内cGMP增加激活。
