β肾上腺素能受体激动剂对离体大鼠肺泡液体清除率的作用

目的探讨β1肾上腺素能受体激动剂地诺帕明、β2肾上腺素能受体激动剂特布他林、β3肾上腺素能受体激动剂BRL37344对离体大鼠肺泡液体清除率(AFC)的作用及机制。方法5%白蛋白等渗生理盐水溶液和不同药物混合后灌注到离体大鼠的肺泡腔内,根据灌注前及其孵育1h后白蛋白浓度的变化来计算大鼠AFC。结果基础AFC为6.9%±2.2%,地诺帕明、特布他林、BRL37344可显著提高AFC(分别为17.1%±2.4%、19.5%±1.2%、19.9%±2.5%)。β1肾上腺素能受体阻滞剂Atenolol可完全抑制地诺帕明提高AFC(6.1%±0.9%)的作用,但不能阻滞特布他林和BRL37344的作用。β2肾上腺素能受体阻滞剂ICI118551完全抑制了特布他林和BRL37344提高AFC(分别为5.7%±0.6%和7.8%±2.6%)的作用,部分抑制了地诺帕明的作用(AFC为12.7%±1.8%)。β3肾上腺素能受体阻滞剂SR59230A部分抑制了BRL37344和特布他林的作用(AFC分别为13.8%±3.1%和14.5%±3.4%),但不能阻滞地诺帕明的作用。结论地诺帕明、特布他林、BRL37344可以显著提高大鼠的AFC。但地诺帕明和特布他林是分别通过β1、β2肾上腺素能受体起作用;而BRL37344可能是通过β2肾上腺素能受体调节的。ICI118551和SR59230A可能分别具有抑制β1或β2肾上腺素能受体的作用。

Effects of β-adrenergic agonists on alveolar fluid clearance in rat lungs

OBJECTIVE: To study the effects of three selective beta-adrenergic agonists on alveolar fluid clearance (AFC) in the isolated rat lungs. METHODS: Isotonic 5% albumin solutions with different pharmacological agents were instilled into the distal airways in the isolated rat lungs. The lungs were inflated with 100% oxygen at 7 cm H2O (1 cm H2O = 0.098 kPa) and placed in a humid incubator at 37 degrees C. AFC was estimated by the progressive increase in the albumin concentration over 1 h. RESULTS: The baseline AFC was 6.9% +/- 2.2%. Beta(1)-adrenergic agonist denopamine, beta(2)-adrenergic agonist terbutaline and beta(3)-adrenergic agonist BRL-37344 increased AFC significantly (17.1% +/- 2.4%, 19.5% +/- 1.2% and 19.9% +/- 2.5%, respectively). Beta(1)-adrenergic antagonist atenolol abolished the effects of denopamine (AFC was 6.1% +/- 0.9%), but did not inhibit the effects of terbutaline and BRL-37344. Beta(2)-adrenergic antagonist ICI-118551 abolished the effects of terbutaline and BRL-37344 (AFC were 5.7% +/- 0.6% and 7.8% +/- 2.6%), and also partially inhibited the effects of denopamine (AFC was 12.7% +/- 1.8%). Beta(3)-adrenergic antagonist SR-59230A partially inhibited the effects of BRL-37344 and terbutaline (AFC were 13.8% +/- 3.1% and 14.5% +/- 3.5%), but did not change the effects of denopamine. CONCLUSIONS: Denopamine, terbutaline and BRL-37344 are potent stimulators of AFC in the rat lungs. The effects of denopamine and terbutaline are mediated via beta(1)- and beta(2)-adrenoceptors, respectively. The effects of BRL-37344 may be mediated via beta(2)-adrenoceptors. ICI-118551 and SR-59230A may have some beta(1)- and beta(2)-inhibitory effects, respectively.