Chronic β-adrenoceptor antagonists upregulate the rat alveolar macrophage adrenergic system through the β1-subtype

Previous studies demonstrate that macrophages synthesis and release catecholamines, which regulate the immune responses in an autocrine manner. These responses are mediated in part by β-adrenoceptors expressed on macrophages. Some β-adrenoceptor antagonists are commonly used in clinical conditions. Here we investigated whether the chronic administration of β-adrenoceptor antagonists upregulate adrenergic system of alveolar macrophage and the potential mechanims.

Propranolol (30 mg/kg·d) or atenolol (5 mg/kg·d) was administered by gavage to rats for 4 weeks. Then alveolar macrophages were isolated and the expression of β(1) or β(2)-adrenoceptor was detected by flow cytometric analysis. Dopamine β-hydroxylase expression was assessed by Western blot assay and the concentrations of noradrenaline, IL-6, and TNF-α in cell supernatants were measured using ELISA after 2 h or 24 h exposure of alveolar macrophages to 100 ng/ml lipopolysaccharide (LPS).

Propranolol increased the mean fluorescence intensity (MFI) of β(1), β(2)-adrenoceptor and the frequency of β(1)-,β(2)- adrenoceptor positive macrophages. However, only the MFI of β(1)-adrenoceptor and the frequency of β(1)-adrenoceptor positive macrophages were increased by atenolol. Furthermore, both propranolol and atenolol promoted LPS-mediated dopamine β-hydroxylase protein expression and increased noradrenaline production in rat alveolar macrophages. This was accompanied by increased LPS-mediated IL-6 and TNF-α production in cell supernatants of alveolar macrophages.

These findings demonstrate that propranolol or atenolol upregulates alveolar macrophage adrenergic system, and the response may be β(1)-adrenergic receptor subtype dependent.