brl-37344 and Pulmonary-Edema

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.. 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.. 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.. These findings suggest that beta(3)-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.

Topics: Adrenergic beta-Agonists; Animals; Body Fluids; Ethanolamines; Hypoxia; Male; Propanolamines; Pulmonary Alveoli; Pulmonary Edema; Rats; Rats, Wistar

To study the effects of three selective beta-adrenergic agonists on alveolar fluid clearance (AFC) in the isolated rat lungs.. Isotonic 5% albumin solutions with different pharmacological agents were instilled into the distal airways in the isolated rat lungs. The lungs were inflated with 100% oxygen at 7 cm H2O (1 cm H2O = 0.098 kPa) and placed in a humid incubator at 37 degrees C. AFC was estimated by the progressive increase in the albumin concentration over 1 h.. The baseline AFC was 6.9% +/- 2.2%. Beta(1)-adrenergic agonist denopamine, beta(2)-adrenergic agonist terbutaline and beta(3)-adrenergic agonist BRL-37344 increased AFC significantly (17.1% +/- 2.4%, 19.5% +/- 1.2% and 19.9% +/- 2.5%, respectively). Beta(1)-adrenergic antagonist atenolol abolished the effects of denopamine (AFC was 6.1% +/- 0.9%), but did not inhibit the effects of terbutaline and BRL-37344. Beta(2)-adrenergic antagonist ICI-118551 abolished the effects of terbutaline and BRL-37344 (AFC were 5.7% +/- 0.6% and 7.8% +/- 2.6%), and also partially inhibited the effects of denopamine (AFC was 12.7% +/- 1.8%). Beta(3)-adrenergic antagonist SR-59230A partially inhibited the effects of BRL-37344 and terbutaline (AFC were 13.8% +/- 3.1% and 14.5% +/- 3.5%), but did not change the effects of denopamine.. Denopamine, terbutaline and BRL-37344 are potent stimulators of AFC in the rat lungs. The effects of denopamine and terbutaline are mediated via beta(1)- and beta(2)-adrenoceptors, respectively. The effects of BRL-37344 may be mediated via beta(2)-adrenoceptors. ICI-118551 and SR-59230A may have some beta(1)- and beta(2)-inhibitory effects, respectively.

Topics: Adrenergic beta-Agonists; Animals; Ethanolamines; In Vitro Techniques; Male; Propanolamines; Pulmonary Alveoli; Pulmonary Edema; Rats; Rats, Sprague-Dawley