Protective effect of endogenous β-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice

Abstract

A. Matthay. Protective effect of endogenous ␤-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice. Am J Physiol Lung Cell Mol Physiol 290: L769 -L776, 2006. First published November 11, 2005 doi:10.1152/ajplung.00334.2005.-Some investigators have reported that endogenous ␤-adrenoceptor tone can provide protection against acute lung injury. Therefore, we tested the effects of ␤-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. ␤-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 ␤-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 ␤-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. Escherichia coli; alveolar fluid clearance; pulmonary edema; ␤-adrenoceptor inhibition; sodium channel EARLIER EXPERIMENTAL WORK established that elevated endogenous epinephrine levels can increase the capacity of the alveolar epithelium to remove alveolar edema fluid in the setting of septic or hemorrhagic shock (29,35,36) or after an acute neurogenic insult (18). However, the effects of endogenous ␤-adrenoceptor tone on lung fluid balance have not been studied in acute severe bacterial pneumonia, the most common cause of clinical acute lung injury (10). We would predict that an acute elevation in endogenous epinephrine and norepinephrine levels during acute bacterial pneumonia might elevate alveolar fluid clearance by cAMP-dependent mechanisms (3, 7, 8, 16, 22-24, 33, 37), providing the alveolar epithelial barrier has not been severely damaged by the bacteria or their products. Some investigations have suggested that endogenous ␤-adrenoceptor stimulation may downregulate ...

A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice

“…Consistent with these studies (45,46), plasma epinephrine levels were elevated during VILI ( Figure 11A). However, no differences between A2BAR -/-mice or their corresponding control mice were observed, suggesting that A2BAR signaling is not involved in VILI-associated increases in plasma epinephrine ( Figure 11B).…”

Transforming Growth Factor β1 Inhibits Cystic Fibrosis Transmembrane Conductance Regulator-dependent cAMP-stimulated Alveolar Epithelial Fluid Transport via a Phosphatidylinositol 3-Kinase-dependent Mechanism

“…Experimental and clinical studies have shown that the cAMP-mediated stimulation of CFTR-dependent alveolar fluid clearance by endogenous or exogenous ␤ 2 AR agonists is one of the major mechanisms that prevent the flooding of the airspaces after onset of ALI (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)23). However, despite the massive release of catecholamines associated with several condi- B, prolonged exposure (6 h) to TGF-␤1 inhibits the epinephrine-dependent PKA activation in polarized rat primary ATII cells.…”

“…Although significant efforts have been made to pharmacologically up-regulate alveolar fluid clearance to reverse the progression of lung injury, these approaches have not been successful (4). ␤ 2 -Adrenergic receptor (␤ 2 AR) agonists have been shown to enhance alveolar epithelial fluid transport via a cAMP-dependent mechanism under physiological conditions (5)(6)(7)(8)(9)(10)(11) and in various experimental models of ALI (12)(13)(14) as well as in one small prospective study in ALI patients (15). However, one of the main limitations of this therapeutic approach is that ␤-adrenergic agonist hyporesponsiveness has been reported in some experimental models of ALI (16,17), although none of the critical mediators of ALI have yet been shown to inhibit the ␤-adrenergic-stimulated fluid transport of the distal lung epithelium.…”

Alveolar Epithelial β2-Adrenergic Receptors

“…There is a great body of experimental data indicating that specific and nonspecific b-agonists enhance AFC in experimental models of cardiogenic and noncardiogenic pulmonary edema (1, 9, 61). Recent data suggest that preservation of b-adrenergic receptor signaling attenuates loss of endothelial cell barrier function in mice with severe bacterial pneumonia (98). Stimulation of b-adrenergic receptors is also capable of preventing hypoxia-induced reduction in alveolar active Na 1 transport and fluid clearance in rats (99).…”