Prolonged isoproterenol infusion impairs the ability of β2-agonists to increase alveolar liquid clearance

2002 ◽  
Vol 282 (4) ◽  
pp. L666-L674 ◽  
Author(s):  
Eric E. Morgan ◽  
Cheryl M. Hodnichak ◽  
Sonya M. Stader ◽  
Kay C. Maender ◽  
John W. Boja ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Prolonged Exposure ◽  
Adrenergic Agonist ◽  
Ringer Lactate ◽  
Alveolar Epithelial ◽  
Atii Cell ◽  
Isoproterenol Infusion ◽  
Β2 Agonists ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

We determined if prolonged isoproterenol (Iso) infusion in rats impaired the ability of the β2-adrenergic agonist terbutaline to increase alveolar liquid clearance (ALC). We infused rats with Iso (at rates of 4, 40, or 400 μg · kg−1 · h−1) or vehicle (0.001 N HCl) for 48 h using subcutaneously implanted miniosmotic pumps. After this time, the rats were anesthetized, and ALC was determined (by mass-balance after instillation of Ringer lactate containing albumin into the lungs) under baseline conditions and after terbutaline administration. Baseline and terbutaline-stimulated ALC in vehicle-infused rats averaged, respectively, 19.6 ± 1.2% (SE) and 44.7 ± 1.5%/h. The ability of terbutaline to increase ALC was eliminated at 400 μg · kg−1 · h−1 Iso, inhibited by 26% at 40 μg · kg−1 · h−1 Iso, and was not affected by 4 μg · kg−1 · h−1 Iso. β-adrenergic receptor (βAR) density of freshly isolated alveolar epithelial type II (ATII) cells from Iso-infused rats was reduced by the 40 and 400 μg · kg−1 · h−1 infusion rates. These data demonstrate that prolonged exposure to β-agonists can impair the ability of β2-agonists to stimulate ALC and produce ATII cell βAR downregulation.

Transforming growth factor-alpha increases alveolar liquid clearance in anesthetized ventilated rats

1996 ◽  
Vol 271 (2) ◽  
pp. L236-L244 ◽  
Author(s):  
H. G. Folkesson ◽  
J. F. Pittet ◽  
G. Nitenberg ◽  
M. A. Matthay
Keyword(s):  
Transforming Growth Factor ◽  
Adrenergic Agonist ◽  
Beta Adrenergic ◽  
Alveolar Epithelial ◽  
Factor Alpha ◽  
Beta Adrenergic Agonist ◽  
Camp Levels ◽  
Na Uptake ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

The effect of transforming growth factor-alpha (TGF-alpha) on alveolar liquid clearance was examined in ventilated, anesthetized rats. An isosmolar Ringer lactate solution with 10, 50, or 200 ng/ml TGF-alpha and 125I-labeled albumin as the alveolar protein tracer was instilled into the right lower lung lobe; the rats were studied for 1 and 4 h. Compared with control rats, addition of 50 ng/ml TGF-alpha to the instilled fluid increased alveolar liquid clearance by 47% over 1 h and by 66% over 4 h (P < 0.05). This increase was similar to the 50% increase in alveolar liquid clearance over 1 h in rats instilled with a beta-adrenergic agonist, salmeterol (28). There was a dose-dependent effect of TGF-alpha (10, 50, 200 ng/ml) on alveolar liquid clearance. The combination of both TGF-alpha and salmeterol did not have an additive effect on alveolar liquid clearance. The TGF-alpha-stimulated increase in alveolar liquid clearance was inhibited by amiloride (10(-4) M), indicating that the increase in clearance depended on increased Na+ uptake across the alveolar epithelium. There was only a twofold increase in intracellular cAMP levels in isolated rat alveolar epithelial type II cells after stimulation with TGF-alpha. In contrast, beta-adrenergic agonist treatment increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels more than tenfold. Genistein (10(-6) M), a tyrosine protein kinase inhibitor, inhibited the TGF-alpha-stimulated increase in alveolar liquid clearance. In summary, TGF-alpha can stimulate in vivo alveolar liquid clearance at a rate similar to beta-adrenergic stimulation by increasing Na+ uptake by alveolar epithelial type II cells. However, the effect may be mediated by a non-cAMP dependent mechanism. Because genistein blocked the increase in alveolar fluid clearance, the signal transduction may involve genistein-dependent phosphorylation.

β-Adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats

2000 ◽  
Vol 89 (4) ◽  
pp. 1255-1265 ◽  
Author(s):  
James A. Frank ◽  
Yibing Wang ◽  
Oscar Osorio ◽  
Michael A. Matthay
Keyword(s):  
Pulmonary Edema ◽  
Left Atrial ◽  
Experimental Studies ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Adrenergic Agonist ◽  
Agonist Therapy ◽  
Arterial Blood ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

To determine whether β-adrenergic agonist therapy increases alveolar liquid clearance during the resolution phase of hydrostatic pulmonary edema, we studied alveolar and lung liquid clearance in two animal models of hydrostatic pulmonary edema. Hydrostatic pulmonary edema was induced in sheep by acutely elevating left atrial pressure to 25 cmH2O and instilling 6 ml/kg body wt isotonic 5% albumin (prepared from bovine albumin) in normal saline into the distal air spaces of each lung. After 1 h, sheep were treated with a nebulized β-agonist (salmeterol) or nebulized saline (controls), and left atrial pressure was then returned to normal. β-Agonist therapy resulted in a 60% increase in alveolar liquid clearance over 3 h ( P< 0.001). Because the rate of alveolar fluid clearance in rats is closer to human rates, we studied β-agonist therapy in rats, with hydrostatic pulmonary edema induced by volume overload (40% body wt infusion of Ringer lactate). β-Agonist therapy resulted in a significant decrease in excess lung water ( P < 0.01) and significant improvement in arterial blood gases by 2 h ( P < 0.03). These preclinical experimental studies support the need for controlled clinical trials to determine whether β-adrenergic agonist therapy would be of value in accelerating the resolution of hydrostatic pulmonary edema in patients.

Halothane and Isoflurane Decrease Alveolar Epithelial Fluid Clearance in Rats 

1998 ◽  
Vol 88 (3) ◽  
pp. 751-760 ◽  
Author(s):  
Saida Rezaiguia-Delclaux ◽  
Christian Jayr ◽  
Deng Feng Luo ◽  
Nor-Eddine Saidi ◽  
Michel Meignan ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Intratracheal Instillation ◽  
Alveolar Fluid Clearance ◽  
Albumin Solution ◽  
Alveolar Epithelial ◽  
Control Value ◽  
Primary Mechanism ◽  
Lung Liquid ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

Background Active sodium transport is the primary mechanism that drives alveolar fluid clearance. In the current study, the effects of exposure to halothane and isoflurane on alveolar fluid clearance in rats were evaluated. Methods Rats were exposed to either halothane (0.4% for 6 h or 2% for 2 h) or isoflurane (0.6% for 6 h or 2.8% for 2 h). Reversibility of halothane effects was assessed after 2 h of exposure to 2% halothane. Alveolar and lung liquid clearance were measured by intratracheal instillation of a 5% albumin solution with 1.5 microCi of 125I-albumin, during mechanical ventilation with 100% FiO2 and the halogenated agent. The effect of terbutaline (10(-4) M) added to the albumin solution was tested after 2 h of exposure to 2% halothane. The increase in protein concentration in the airspaces over 1 h was used to evaluate alveolar liquid clearance. Lung liquid clearance was calculated gravimetrically. Results Alveolar liquid clearance rates were decreased by 24%, 30% and 40% compared with controls (P &lt; 0.05) after 2 h of exposure to halothane, 6 h of exposure to halothane, and 6 h of exposure to isoflurane, respectively. After 2 h of exposure to isoflurane, alveolar liquid clearance did not change. In the 2-h halothane exposure group, alveolar liquid clearance returned to the control value 2 h after withdrawal of halothane. Terbutaline increased alveolar liquid clearance by 50% and 89% in the control and 2-h halothane exposure groups, respectively. In all experiments, the same results were obtained for alveolar and lung liquid clearance. Conclusions Halothane and isoflurane caused a reversible decrease in alveolar epithelial fluid clearance. Two hours of exposure to halothane did not alter the stimulatory effect of terbutaline on alveolar liquid clearance.

Alveolar endotoxin increases alveolar liquid clearance in rats

1995 ◽  
Vol 79 (6) ◽  
pp. 2021-2028 ◽  
Author(s):  
C. Garat ◽  
S. Rezaiguia ◽  
M. Meignan ◽  
M. P. D'Ortho ◽  
A. Harf ◽  
...  
Keyword(s):  
Alveolar Epithelial Cells ◽  
Alveolar Fluid Clearance ◽  
Albumin Solution ◽  
Biologically Relevant ◽  
Alveolar Epithelial ◽  
Pathological Conditions ◽  
Lung Epithelial Permeability ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

Under some pathological conditions, ion transport across alveolar epithelial cells is downregulated, whereas under other pathological conditions, it may be upregulated. Because endotoxin is a biologically relevant pathological stimulus, we investigated the effect of endotoxin on alveolar epithelial liquid clearance in vivo. Escherichia coli endotoxin (220 micrograms/kg) was instilled into the lungs via the trachea of rats. Then, 24 or 40 h after endotoxin instillation, alveolar and lung liquid clearances were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 ml/kg into both lungs). Alveolar liquid clearance was significantly greater at 24 h (36 +/- 5%) and 40 h (38 +/- 7%) after endotoxin exposure than in saline-instilled controls (27 +/- 6%). Although there was an influx of neutrophils into the air space, there was no increase in lung epithelial permeability to protein at 24 or 40 h. Amiloride (2 x 10(-3) M), a sodium channel inhibitor, significantly reduced alveolar liquid clearance in the rats exposed to endotoxin. However, the increase in alveolar liquid clearance was not inhibited when propranolol (2 x 10(-5) M) was added to the 5% albumin solution. Thus exposure to alveolar endotoxin upregulates net alveolar fluid clearance in vivo for up to 40 h, a potentially important mechanism for accelerating alveolar fluid clearance under some pathological conditions. The increase in alveolar liquid clearance 24 and 40 h after instillation of endotoxin into the air spaces is mediated by an increased uptake of sodium through amiloride-sensitive sodium channels.

Inhibition of β-adrenergic-dependent alveolar epithelial clearance by oxidant mechanisms after hemorrhagic shock

1999 ◽  
Vol 276 (5) ◽  
pp. L844-L857 ◽  
Author(s):  
K. Modelska ◽  
M. A. Matthay ◽  
L. A. S. Brown ◽  
E. Deutch ◽  
L. N. Lu ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Alveolar Epithelium ◽  
Albumin Solution ◽  
Epithelial Lining Fluid ◽  
Alveolar Epithelial ◽  
Major Alteration ◽  
Endogenous Release ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

Endogenous release of catecholamines is an important mechanism that can prevent alveolar flooding after brief but severe hemorrhagic shock. The objective of this study was to determine whether this catecholamine-dependent mechanism upregulates alveolar liquid clearance after prolonged hemorrhagic shock. Rats were hemorrhaged to a mean arterial pressure of 30–35 mmHg for 60 min and then resuscitated with a 4% albumin solution. Alveolar liquid clearance was measured 5 h later as the concentration of protein in the distal air spaces over 1 h after instillation of a 5% albumin solution into one lung. There was no upregulation of alveolar liquid clearance after prolonged hemorrhagic shock and fluid resuscitation despite a significant increase in plasma epinephrine levels. The intravenous or intra-alveolar administration of exogenous catecholamines did not upregulate alveolar liquid clearance. In contrast, catecholamine-mediated upregulation of alveolar liquid clearance was restored either by depletion of neutrophils with vinblastine, by the normalization of the concentration of reduced glutathione in the alveolar epithelial lining fluid by N-acetylcysteine, or by the inhibition of the conversion from xanthine dehydrogenase to xanthine oxidase. These experiments provide the first in vivo evidence that a neutrophil-dependent oxidant injury to the alveolar epithelium prevents the upregulation of alveolar fluid clearance by catecholamines in the absence of a major alteration in paracellular permeability to protein after prolonged hemorrhagic shock.

Alveolar and lung liquid clearance in anesthetized rabbits

1991 ◽  
Vol 70 (4) ◽  
pp. 1827-1835 ◽  
Author(s):  
N. Smedira ◽  
L. Gates ◽  
R. Hastings ◽  
C. Jayr ◽  
T. Sakuma ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Lower Lobe ◽  
Ringer Lactate ◽  
Autologous Plasma ◽  
Beta Adrenergic ◽  
Important Species ◽  
Endogenous Catecholamine ◽  
Lung Liquid ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

Alveolar and lung liquid clearance were studied over 8 h in intact anesthetized ventilated rabbits by instillation of either isosmolar Ringer lactate (2 ml/kg) or autologous plasma (2 or 3 ml/kg) into one lower lobe. The half time for lung liquid clearance of the isosmolar Ringer lactate was 3.3 h and that for plasma clearance was 6 h. In the plasma experiments, the alveolar protein concentration after 1 h was 5.2 +/- 0.8 g/dl, which was significantly greater than the initial instilled protein concentration of 4.3 +/- 0.7 g/dl (P less than 0.05). Thus alveolar protein concentration increased by 21 +/- 12% over 1 h, which matched clearance from the entire lung of 19 +/- 11% of the instilled volume. Overall the rate of alveolar and lung liquid clearance in rabbits was significantly faster than in prior studies in dogs and sheep. The fast alveolar liquid clearance rate in rabbits was not due to higher endogenous catecholamine release, because intravenous and alveolar (5 x 10(-5) M) propranolol did not slow the clearance. Also, beta-adrenergic therapy with alveolar terbutaline (10(-5) or 10(-4) M) did not increase the alveolar or lung liquid clearance rates. Phloridzin (10(-3) M) did not slow alveolar liquid clearance. However, amiloride (10(-4) M) inhibited 75% of the basal alveolar liquid clearance in rabbits, thus providing evidence that alveolar liquid clearance in rabbits depends primarily on sodium-dependent transport. This rabbit study provides further evidence for important species differences in the basal rates of alveolar liquid and solute clearance as well as the response to beta-adrenergic agonists and ion transport inhibitors.

scholarly journals Alveolar liquid clearance in the anesthetized ventilated guinea pig

1998 ◽  
Vol 274 (2) ◽  
pp. L235-L243 ◽  
Author(s):  
Andreas Norlin ◽  
Neelu Finley ◽  
Parisa Abedinpour ◽  
Hans G. Folkesson
Keyword(s):  
Guinea Pigs ◽  
Adrenergic Receptors ◽  
Protein Concentration ◽  
Albumin Solution ◽  
Adrenergic Agonist ◽  
Endogenous Catecholamine ◽  
Alveolar Liquid Clearance ◽  
Stimulation Of ◽  
Alveolar Liquid

Alveolar liquid clearance was examined in ventilated, anesthetized guinea pigs. An isosmolar 5% albumin solution was instilled into the lungs. Alveolar liquid clearance was studied over 1 h and was measured from the increase in alveolar protein concentration as water was reabsorbed. Basal alveolar liquid clearance was 38% of instilled volume. The high basal alveolar liquid clearance was not secondary to endogenous catecholamine release. Compared with control animals, epinephrine and the general β-adrenergic agonist isoproterenol increased alveolar liquid clearance to ∼50% of instilled volume ( P < 0.05), whereas the β2-adrenergic agonist terbutaline was without effect. The stimulation of alveolar liquid clearance by epinephrine or isoproterenol was completely inhibited by the addition of the general β-adrenergic inhibitor propranolol or the β1-adrenergic inhibitor atenolol. Alveolar liquid clearance was inhibited by the sodium-channel inhibitor amiloride by 30–40% in control animals and in animals treated with epinephrine or isoproterenol. Isoproterenol and epinephrine, but not terbutaline, increased adenosine 3′,5′-cyclic monophosphate in in vitro incubated lung tissue. The results suggest that alveolar liquid clearance in guinea pigs is mediated partly through amiloride-sensitive sodium channels and that alveolar liquid clearance can be increased by stimulation of primarily β1-adrenergic receptors.

scholarly journals Impaired alveolar liquid clearance after 48-h isoproterenol infusion spontaneously recovers by 96 h of continuous infusion

2006 ◽  
Vol 291 (2) ◽  
pp. L252-L256 ◽  
Author(s):  
Michael B. Maron ◽  
Hans G. Folkesson ◽  
Sonya M. Stader ◽  
Cheryl M. Hodnichak
Keyword(s):  
Continuous Infusion ◽  
Time Course ◽  
Lung Epithelium ◽  
Osmotic Minipump ◽  
Peripheral Lung ◽  
Distal Lung ◽  
Time Periods ◽  
Isoproterenol Infusion ◽  
Alveolar Liquid Clearance ◽  
Alveolar Liquid

We previously demonstrated that 48-h isoproterenol (Iso) infusion in rats impaired the ability of β-adrenoceptor (β-AR) agonists to increase alveolar liquid clearance (ALC). In this study, we determined whether this impairment persisted over longer time periods by infusing 400 μg·kg−1·h−1 Iso by osmotic minipump for 24–144 h ( n = 6–7/group). ALC in control rats was 19.0 ± 2.4 (SD)% of instilled volume absorbed per hour. In Iso-infused rats, ALC was elevated at 24 h (34.9 ± 2.4%) and decreased at 48 h (15.2 ± 4.4%) and had recovered to 24 h values at 96 h (37.3 ± 3.8%) and 144 h (35.2 ± 3.3%). Plasma Iso concentrations remained elevated at all Iso infusion times. Peripheral lung β2-AR expression exhibited a parallel time course, with a reduction in expression observed at 48 h, followed by an increase to 24 h values at 96 and 144 h. Propranolol prevented the increase in ALC observed at 96 and 144 h, indicating that the recovery in ALC was mediated by a recovery of β-AR function and β-AR signaling. ALC at 96 and 144 h could not be further increased by terbutaline, indicating that ALC was maximally stimulated. These data indicate that recovery of β-AR-stimulated ALC can occur in the continued presence of Iso and is mediated by a recovery of the ability of the distal lung epithelium to respond to β-AR stimulation.

Postreceptor defects in alveolar epithelial β-adrenergic signaling after prolonged isoproterenol infusion

2003 ◽  
Vol 285 (3) ◽  
pp. L578-L583 ◽  
Author(s):  
Eric E. Morgan ◽  
Sonya M. Stader ◽  
Cheryl M. Hodnichak ◽  
Kate E. Mavrich ◽  
Hans G. Folkesson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mass Balance ◽  
Protein Kinase A ◽  
Alveolar Type ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Camp Analog ◽  
Isoproterenol Infusion ◽  
Alveolar Liquid Clearance ◽  
Kinase A

We previously found that prolonged isoproterenol (Iso) infusion in rats impaired the ability of β-adrenoceptor (β-AR) agonists to increase alveolar liquid clearance (ALC). Here, we determined if postreceptor defects in β-AR signaling contribute to this impairment. Iso was infused using subcutaneous miniosmotic pumps (4, 40, or 400 μg · kg-1 · h-1) in rats for 48 h. At this time, forskolin-stimulated ALC was measured by mass balance. Forskolin-stimulated ALC [33.4 ± 2.1%/h (mean ± SE) in vehicle-infused rats] was reduced by 25 and 38%, respectively, after the 40 and 400 μg · kg-1 · h-1 Iso infusions. The ability of forskolin to increase cAMP was reduced by 70% in alveolar type II (ATII) cells isolated from rats infused with 400 μg · kg-1 · h-1 Iso. Additionally, the ability of the stable cAMP analog 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Sp-isomer, to increase ALC (48.7 ± 3.0% in vehicle-infused rats) was reduced by 25 and 51%, respectively, after the 40 and 400 μg · kg-1 · h-1 infusions. Finally, the ability of cAMP to increase protein kinase A activity was eliminated in ATII cells isolated from rats infused with Iso at 400 μg · kg-1 · h-1. These data demonstrate that prolonged β-AR agonist exposure can impair alveolar epithelial β-AR signaling downstream of the β-AR.

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