Effect of beta3-adrenergic agonists on alveolar fluid clearance in hypoxic rat lungs.
BACKGROUND
Recent research suggests that beta(2)-adrenergic agonists increase alveolar fluid clearance (AFC) under physiologic and pathologic conditions. It is unknown whether beta(3)-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of beta(3)-adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved.


METHODS
Hypoxic rats were exposed to 10% oxygen. BRL-37344 (beta(3)-adrenergic agonist) or CGP-12177 (selective beta(3)-adrenergic agonist) alone or combined with beta receptor antagonists, sodium channel blockers, or Na(+)/K(+)-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content (TLW) and AFC were measured.


RESULTS
AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride (a Na(+) channel blocker) and ouabain (a Na(+)/K(+)-ATPase inhibitor) by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177.


CONCLUSIONS
These findings suggest that beta(3)-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.
Li
Nai-jing
NJ
Department of Gerontology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
Li
Wei
W
He
Ping
P
Gu
Xiu
X
Li
Sheng-qi
SQ
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism*; D004983:Ethanolamines / Q000627:therapeutic use*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D011412:Propanolamines / Q000627:therapeutic use*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011412:Propanolamines; C057368:BRL 37344; C033394:CGP 12177