Protective effect of endogenous beta-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice.
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 Escherichia coli pneumonia. Mice were pretreated with propranolol or saline and then intratracheally instilled with live E. coli (10(7) colony-forming units). 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 histological evidence of acute pulmonary inflammation, arterial hypoxemia, a threefold 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 because plasma macrophage inflammatory protein-2 levels were higher in the propranolol pretreatment group compared with controls. The decrease in alveolar fluid clearance with propranolol was explained by a decrease in catecholamine-stimulated fluid clearance. 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: 1) reducing lung vascular injury and 2) upregulating the resolution of alveolar edema.
Su
Xiao
X
Cardiovascular Research Institute, Univ. of California, San Francisco, CA 94143-0130, USA. xiao.su@ucsf.edu
Robriquet
Laurent
L
Folkesson
Hans G
HG
Matthay
Michael A
MA
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D054426:Chemokine CXCL2; D018925:Chemokines / Q000097:blood; D004837:Epinephrine / Q000097:blood; D053503:Epithelial Sodium Channels; D004926:Escherichia coli / Q000254:growth & development; D004927:Escherichia coli Infections / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005740:Gases / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D018410:Pneumonia, Bacterial / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D011312:Pressure; D011433:Propranolol / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012964:Sodium / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D053503:Epithelial Sodium Channels; D005740:Gases; D011943:Receptors, Adrenergic, beta; D015222:Sodium Channels; D000584:Amiloride; D012964:Sodium; D011433:Propranolol; D004837:Epinephrine