Effects of α_1-, β_1-, β_2-, β_3-Adrenergic Agonists on Alveolar Fluid Clearance in Isolated Rat Lungs

  • Gu Xiu
    Division of Thoracic Surgery, Kanazawa Medical University
  • Sugita Makoto
    Division of Thoracic Surgery, Kanazawa Medical University
  • Sagawa Motoyasu
    Division of Thoracic Surgery, Kanazawa Medical University
  • Sakuda Maki
    Division of Respiratory Medicine, Kanazawa Medical University
  • Osanai Kazuhiro
    Division of Respiratory Medicine, Kanazawa Medical University
  • Toga Hirohisa
    Division of Respiratory Medicine, Kanazawa Medical University
  • Sakuma Tsutomu
    Division of Thoracic Surgery, Kanazawa Medical University

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Objective The objective of this study was to determine if α_1-, β_1-, β_2- and, β_3-adrenergic agonists stimulated alveolar fluid clearance in the isolated rat lungs and to determine the mechanism responsible for their effects. Methods Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the distal airways in the isolated rat lungs. The lungs were inflated with 100% oxygen at 7cm H_2O and placed in a humid incubator at 37℃. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 hour after instillation. Results Basal alveolar fluid clearance was 6.9±2.2%/h of instilled volume. Phenylephrine (an α_1-adrenergic agonist) increased alveolar fluid clearance by 109%. Prazosin (a selective α_1 adrenergic antagonist) and ICI-118551 (a β_2-adrenergic antagonist) significantly inhibited the increase in alveolar fluid clearance caused by phenylephrine, whereas yohimbine (an α_2-adrenergic antagonist) did not. Denopamine (a β_1-radrenergic agonist), terbutaline (a β_2-adrenergic agonist), and BRL-37344 (a β_3-adrenergic agonist) increased alveolar fluid clearance. Atenolol (a β_1-adrenergic antagonist) abolished the effect of denopamine, but did not inhibit the effects of terbutaline and BRL-37344. ICI-118551 abolished the effect of terbutaline and BRL-37344, and also inhibited the effects of denopamine in part. SR-59230A (a β_3-adrenergic antagonist) inhibited the effects of BRL-37344 and terbutaline in part, but did not change the effect of denopamine. Conclusions These results indicate that phenylephrine, denopamine, terbutaline and BRL-37344 are potent stimulators of alveolar fluid clearance in the rat lungs. The increase in alveolar fluid clearance caused by phenylephrine can be mediated via α_1-adrenoceptors. The effects of denopamine and terbutaline are mediated via β_1-and β_2-adrenoceptors, respectively. The effects of BRL-37344 may be mediated via β_2-adrenoceptors.

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