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Am J Physiol Lung Cell Mol Physiol (November 11, 2005). doi:10.1152/ajplung.00334.2005
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Submitted on July 29, 2005
Accepted on November 3, 2005

Protective Effect of Endogenous {beta}-Adrenergic Tone on Lung Fluid Balance in Acute Bacterial Pneumonia in Mice

Xiao Su1*, Laurent Robriquet1, Hans G Folkesson2, and Michael A Matthay1

1 University of California San Francisco, Cardiovascular Research Institute, San Francisco, CA, USA
2 Northeastern Ohio Universities College of Medicine, Department of Physiology and Pharmacology, Rootstown, OH, USA

* To whom correspondence should be addressed. E-mail: xiao.su{at}ucsf.edu.

Some investigators have reported that endogenous {beta}-adrenoceptor tone can provide protection against acute lung injury. Therefore, we tested the effects of {beta}-adrenoceptor inhibition in mice with acute E. coli pneumonia. Mice were pretreated with propranolol or saline and then intratracheally instilled with live E. coli (107cfu). Hemodynamics, arterial blood gases, plasma catecholamines, extravascular lung water, lung permeability to protein, bacterial counts, and alveolar fluid clearance were measured. Acute E. coli pneumonia was established after 4 h with histologic evidence of acute pulmonary inflammation, arterial hypoxemia, a 3-fold increase in lung vascular permeability, and a 30% increase in extravascular lung water as an increase in plasma catecholamine levels. {beta}-adrenoceptor inhibition resulted in a marked increase in extravascular lung water that was explained by both an increase in lung vascular permeability and a reduction in net alveolar fluid clearance. The increase in extravascular lung water with propranolol pretreatment was not explained by an increase in systemic or vascular pressures. The increase in lung vascular permeability was explained in part by anti-inflammatory effects of {beta}-adrenoceptor stimulation since plasma MIP-2 levels were higher in propranolol pretreatment group compared to the controls. The decrease in alveolar fluid clearance with propranolol was explained by a decrease in catecholamines stimulated fluid clearance. Taken together, these results indicate that endogenous {beta}-adrenoceptor tone has a protective effect in limiting accumulation of extravascular lung water in acute severe E. coli pneumonia in mice by two mechanisms: (i) reducing lung vascular injury and (ii) upregulating the resolution of alveolar edema.




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