Targeted transgenic expression of beta(2)-adrenergic receptors to type II cells increases alveolar fluid clearance

Clearance of edema fluid from the alveolar space can be enhanced by endogen ous and exogenous beta -agonists. To selectively delineate the effects of a lveolar type II (ATII) cell beta (2)-adrenergic receptors (beta (2)-ARs) on alveolar fluid clearance (AFC), we generated transgenic (TG) mice that ove rexpressed the human beta (2)-AR under control of the rat surfactant protei n C promoter. In situ hybridization showed that transgene expression was co nsistent with the distribution of ATII cells. TG mice expressed 4.8-fold gr eater beta (2)-ARs than nontransgenic (NTG) mice (939 +/- 113 vs. 194 +/- 1 8 fmol/mg protein; P < 0.001). Basal AFC in TG mice was <similar to>40% gre ater than that in untreated NTG mice (15 +/- 1.4 vs. 10.9 +/- 0.6%; P < 0.0 05) and approached that of NTG mice treated with the <beta>-agonist formote rol (19.8 +/- 2.2%; P = not significant), Adrenalectomy decreased basal AFC in TG mice to 9.7 +/- 0.5% but had no effect on NTG mice (11.5 +/- 1.0%). Na+-K+- ATPase alpha (1)-isoform expression was unchanged, whereas alpha (2 )-isoform. expression was similar to 80% greater in the TG mice. These find ings show that beta (2)-AR overexpression can be an effective means to incr ease AFC in the absence of exogenous agonists and that AFC can be stimulate d by activation Of beta (2)-ARs specifically expressed on ATII cells.