Chapman D L, Carlton D P, Cummings J J, Poulain F R, Bland R D
Cardiovascular Research Institute, University of California, San Francisco 94143.
Pediatr Res. 1991 Apr;29(4 Pt 1):357-61. doi: 10.1203/00006450-199104000-00006.
To see if phosphodiesterase inhibition might enhance the effect of beta-adrenergic stimulation on fetal lung liquid secretion, we studied the independent and combined effects of intrapulmonary terbutaline and aminophylline on net production of lung luminal liquid over time (Jv) in fetal lambs with chronically placed tracheal loop catheters. We calculated Jv during baseline and experimental periods (90-120 min each) by measuring serial concentrations of 125I-albumin, an impermeant tracer that was well mixed in the luminal liquid. In 21 experiments, tracheal instillation of terbutaline (10(-5) M) decreased Jv from 11 +/- 1 (mean +/- SEM) to -3 +/- 2 mL/h. In six other studies, aminophylline (10(-3) M) alone had no significant effect on Jv. In 12 experiments, we gave the two drugs sequentially: terbutaline decreased Jv from 11 +/- 2 to -3 +/- 2 mL/h and aminophylline further decreased Jv to -8 +/- 2 mL/h. Amiloride (10(-4) M), an inhibitor of epithelial Na+ transport, reversed the combined effect of terbutaline and aminophylline, increasing Jv to 8 +/- 1 mL/h. Thus, phosphodiesterase inhibition enhances the beta-adrenergic effect of terbutaline on Na(+)-dependent absorption of liquid from the lung lumen of fetal lambs.
为了探究磷酸二酯酶抑制是否可能增强β-肾上腺素能刺激对胎儿肺液分泌的作用，我们使用长期放置气管环导管的胎羊，研究了肺内特布他林和氨茶碱对肺腔液体净生成量随时间变化（Jv）的独立及联合作用。我们通过测量125I-白蛋白的系列浓度来计算基线期和实验期（各90 - 120分钟）的Jv，125I-白蛋白是一种不渗透的示踪剂，在腔液中充分混合。在21次实验中，气管内滴注特布他林（10^(-5) M）使Jv从11±1（均值±标准误）降至 - 3±2 mL/h。在其他6项研究中，单独使用氨茶碱（10^(-3) M）对Jv无显著影响。在12次实验中，我们依次给予这两种药物：特布他林使Jv从11±2降至 - 3±2 mL/h，氨茶碱进一步使Jv降至 - 8±2 mL/h。上皮钠转运抑制剂氨氯吡咪（10^(-4) M）逆转了特布他林和氨茶碱的联合作用，使Jv增至8±1 mL/h。因此，磷酸二酯酶抑制增强了特布他林对胎羊肺腔液体钠依赖性吸收的β-肾上腺素能效应。
