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  • Title: Beta1-adrenoceptor stimulation by high-dose terbutaline downregulates terbutaline-stimulated alveolar fluid clearance in ex vivo rat lung.
    Author: Sakuma T, Tuchihara C, Ishigaki M, Osanai K, Nambu Y, Toga H, Takahashi K, Ohya N, Inoue M, Matthay MA.
    Journal: Exp Lung Res; 2001; 27(5):453-68. PubMed ID: 11480585.
    Abstract:
    Because high-dose terbutaline and isoproterenol (10(-3) M), beta2-adrenergic agonists, failed to increase alveolar fluid clearance, the mechanisms responsible for this effect were examined in ex vivo rat lungs. An isosmolar 5% albumin solution with Evans blue dye was instilled into the distal airspaces in isolated rat lungs that were then inflated with 100% oxygen at an airway pressure of 8 cm H2O in a 37 degrees C incubator. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1 hour. The results indicated that: (1) although 10(-5) M terbutaline or isoproterenol increased alveolar fluid clearance, 10(-3) M terbutaline or isoproterenol did not; (2) both concentrations of terbutaline (10(-5), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate in cultured type II alveolar epithelial cells; (3) instillation of atenolol, a selective beta1-adrenergic antagonist, in the presence of either 10(-3) M terbutaline or isoproterenol was associated with an increase in alveolar fluid clearance. These results suggested that beta1-adrenoceptor stimulation prevented the normal response to a beta2-adrenergic agonist. To further test this hypothesis, a selective beta1-adrenergic agonist, denopamine, was administered; these results showed that (4) 10(-3) M denopamine, a selective beta1-adrenergic agonist, inhibited the increase in alveolar fluid clearance in the presence of 10(-5) M terbutaline; (5) hypoxia for 2 hours did not alter the effects of terbutaline on alveolar fluid clearance. The mechanism for the inability of the alveolar epithelium to respond to high-dose terbutaline or isoproterenol with the normal upregulation of alveolar fluid clearance in ex vivo rats lungs appears to be mediated by beta1-adrenoceptor stimulation that subsequently suppresses the beta2-adrenergic response.
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