Effects of lung inflation on alveolar epithelial solute and water transport properties

1982 ◽  
Vol 52 (6) ◽  
pp. 1498-1505 ◽  
Author(s):  
K. J. Kim ◽  
E. D. Crandall

Paired hollow bullfrog lungs (Rana catesbeiana) were used to study the effects of lung inflation on alveolar epithelial transport of water and hydrophilic solutes. Frogs were double pithed and the lungs were removed after bronchial placement of a Lucite plug. Three openings in the plug accommodated the insertion of two agar-Ringer bridges (for electrical potential measurement and passage of direct current) and the injection and removal of alveolar bathing fluid. Ringer solution containing a tracer quantity of radioactive solute was instilled into the lung sacs (5 ml or 50 ml) and the lungs were suspended in baths of Ringer solution containng appropriate cold solutes (5 mM). Permeability properties of each solute (and water) were determined from the rate of radiotracer concentration change in the bath. The spontaneous potential difference, tissue resistance, and solute permeability properties determined in these experiments showed no significant differences between the 5- and 50-ml lungs. Assuming homogeneous, cylindrical water-filled pores to be present in the tissue, the equivalent pore radii estimated from the rates of solute and water fluxes were 1.1 (for 5-ml lungs) and 0.9 nm (for 50-ml lungs). After overinflation of the lung (to greater than 80 ml), experiments at 50 ml yielded a pore radius of 3.4 nm. These data suggest that passive alveolar epithelial transport properties do not change with degrees of lung inflation normally encountered in vivo but that overinflation can lead to increased leakiness of the barrier.

1980 ◽  
Vol 49 (6) ◽  
pp. 1032-1036 ◽  
Author(s):  
E. A. Egan

The relation between the solute permeability of th alveolar epithelium, characterized as a pore radius, and lung inflation was studied in anesthetized dogs. Pore radius was calculated from measurements of the rate of efflux of several radiolabeled solutes of known molecular size from alveolar saline. Individual animals were studied at two or more separate inflation volumes. The pore radius during the first volume studied averaged 20 A in high-volume animals (mean inflation 82% of capacity) and 15 A at lower volume (mean inflation, 47% of capacity). The difference was significantly P < 0.05. Lungs inflated to total capacity showed free solute movement across the lung epithelium. Increasing inflation volume in an animal always produced a larger pore radius. Decreasing the inflation volume did not produce a smaller pore radius; it remained the same or became larger. Volume induced increases in lung epithelial solute permeability do not reverse immediately at lower volumes, suggesting this phenomenon represents lung injury.


2007 ◽  
Vol 102 (2) ◽  
pp. 794-802 ◽  
Author(s):  
Nicolas de Prost ◽  
Didier Dreyfuss ◽  
Georges Saumon

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of111In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 ± 4.69 and 22.2 ± 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space (111In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.


1979 ◽  
Vol 237 (1) ◽  
pp. R74-R79 ◽  
Author(s):  
T. C. Cox ◽  
R. H. Alvarado

Carefully dissected, mounted, and bathed with Ringer solution, the larval bullfrog skin has a resistance of about 9,000 omega.cm2 and a stable transepithelial electrical potential of about 20 mV (inside +). A short-circuit current of about 2 microA.cm-2 is generated that is comparable in magnitude to the net inward flux of Na+. At open circuit the flux ratio equation for Na+ is not satisfied. Larval skin is less sensitive to ouabain, amiloride, and ADH than adult skin. The current-voltage (C-V) relationship across the preparation is not linear; there are distinct breaks in both the hyperpolarizing and hypopolarizing regions. The former break, at about +130 mV, corresponds with a break observed in adult skin that corresponds with ENa. The shunt resistance (RS) and active pathway resistance (RA) were estimated by C-V curve analysis and by ion substitution. The two methods yielded comparable values with RS about 11 k omega.cm2 and RA about 62 k omega.cm2. It is suggested that transport is limited by the number of entry sites for sodium at the apical border of transport cells.


1983 ◽  
Vol 244 (1) ◽  
pp. R58-R65
Author(s):  
T. C. Cox ◽  
R. H. Alvarado

Transport and electrical characteristics of the isolated skin of larval Rana catesbeiana were analyzed using ion substitution and nystatin. When the inner (IBS) and outer (OBS) bathing solutions contained Na Ringer solution the electrical potential (TEP), short-circuit current (SCC), and resistance (R2) were 23.5 +/- 7.0 mV, 2.8 +/- 0.7 microA . cm-2, and 8.00 +/- 0.74 k omega. cm2, respectively (n = 4). When K was substituted for Na in the OBS these values were not changed significantly. When nystatin (120 U.cm-3), a drug that increases the permeability of membranes to small cations, was added to the OBS (Na Ringer) there was a striking increase in the TEP to 52.8 +/- 3.1 mV, SCC to 14.8 +/- 2.0 microA . cm-2, and drop in R2 to 3.75 +/- 0.52 k omega . cm2. The response to nystatin was similar with Na or K Ringer solution in the OBS (Na Ringer in the IBS). With Na Ringer in the OBS and IBS, the increase in SCC induced by low doses of nystatin equaled net Na flux measured isotopically. Plots of transepithelial conductance against SCC after nystatin were linear and provided estimates of shunt resistance (R*sh = 14.6 +/- 1.3 k omega . cm2) and electromotive driving force for ions (E*A = 76 +/- 3 mV). Similar curves were obtained with K Ringer in the OBS. In the presence of nystatin, characteristics of the basolateral membrane were evaluated. It displayed selective permeability to K relative to Na or Tris.


1987 ◽  
Vol 253 (4) ◽  
pp. F613-F621 ◽  
Author(s):  
N. Y. Marcus ◽  
D. C. Marcus

The isolated nonsensory region of the gerbil utricle in vitro produced a lumen-positive transepithelial electrical potential difference (VT) of +5.7 mV and a luminal fluid containing 106 mM K when bathed in mammalian Ringer solution (5 mM K and 150 mM Na). The lumen of this region was perfused in vitro with K-free solution and the luminal [K], VT, and transepithelial resistance (RT) were measured before and following perfusion under control conditions and after addition of bumetanide (0.1 mM) or ouabain (1 mM) to the bath. The perfusate contained a reduced [Ca], since the average value of utricular endolymph in vivo (0.28 +/- 0.03 mM) measured with Ca-selective microelectrodes was 38% of that in perilymph. Under control conditions, the luminal [K] initially increased at a rate of 2.13 mumol X cm-2 X h-1 after perfusion; net secretion continued until the luminal [K] returned to its preperfusion level. This flux rate corresponds to 57 microA/cm2. The “equivalent short-circuit current” (Equiv. Isc; VT/RT) was found to average 61 microA/cm2. Both K secretion and VT were fully inhibited by bumetanide and by ouabain. Luminal application of Ba (5 mM) in K-free solution had no effect on the initial rate of K secretion, but did prevent full recovery of luminal [K] to the control level. These results are the first estimates of K secretion by the nonsensory cells of the utricle and are the first to directly demonstrate inhibition of K secretion in the inner ear by bumetanide and in the nonsensory tissue of the utricle by ouabain.


2014 ◽  
Vol 307 (7) ◽  
pp. L524-L536 ◽  
Author(s):  
Hidenori Kage ◽  
Per Flodby ◽  
Danping Gao ◽  
Yong Ho Kim ◽  
Crystal N. Marconett ◽  
...  

Claudins are tight junction proteins that regulate paracellular ion permeability of epithelium and endothelium. Claudin 4 has been reported to function as a paracellular sodium barrier and is one of three major claudins expressed in lung alveolar epithelial cells (AEC). To directly assess the role of claudin 4 in regulation of alveolar epithelial barrier function and fluid homeostasis in vivo, we generated claudin 4 knockout (Cldn4 KO) mice. Unexpectedly, Cldn4 KO mice exhibited normal physiological phenotype although increased permeability to 5-carboxyfluorescein and decreased alveolar fluid clearance were noted. Cldn4 KO AEC monolayers exhibited unchanged ion permeability, higher solute permeability, and lower short-circuit current compared with monolayers from wild-type mice. Claudin 3 and 18 expression was similar between wild-type and Cldn4 KO alveolar epithelial type II cells. In response to either ventilator-induced lung injury or hyperoxia, claudin 4 expression was markedly upregulated in wild-type mice, whereas Cldn4 KO mice showed greater degrees of lung injury. RNA sequencing, in conjunction with differential expression and upstream analysis after ventilator-induced lung injury, suggested Egr1, Tnf, and Il1b as potential mediators of increased lung injury in Cldn4 KO mice. These results demonstrate that claudin 4 has little effect on normal lung physiology but may function to protect against acute lung injury.


1982 ◽  
Vol 243 (5) ◽  
pp. G348-G358 ◽  
Author(s):  
G. Flemstrom ◽  
A. Garner ◽  
O. Nylander ◽  
B. C. Hurst ◽  
J. R. Heylings

Duodenal surface epithelial transport of HCO3(-) was measured by direct titration in anesthetized animals. Alkalinization of the lumen occurred in all species, although basal rates varied considerably: rats (approximately 10), cats (approximately 15), pigs (approximately 25), dogs (approximately 25), guinea pigs (approximately 40), and rabbits (approximately 170 mueq.cm-1.h-1). In cats duodenum transported HCO3(-) at a greater basal rate than jejunum (approximately 5 mueq.cm-2.h-1) and developed a higher transmucosal electrical potential difference (PD, lumen negative). Luminal application of 10 mM HCl for 5 min produced a sustained increase in the rate of duodenal HCO3(-) transport that was accompanied by a rise in appearance of E-like prostaglandin immunoreactivity in the lumen and a decrease in DNA release. In cats pretreated with indomethacin (10 mg/kg iv), acid caused only a transient increase in HCO3(-) transport. Exogenous prostaglandin E2 (1-12 microM, luminal) increased basal HCO3(-) transport in cats, rats, and dogs but had no effect on this transport in guinea pigs and rabbits. However, prostaglandin E2 increased HCO3(-) transport and PD in guinea pigs pretreated with inhibitors of tissue cyclooxygenase activity (indomethacin or aspirin) or gastric H+ secretion (cimetidine). Thus the continuous exposure of the duodenum of herbivores to HCl discharged from the stomach may itself stimulate HCO3(-) transport via an increase in endogenous prostaglandin levels and render exogenous prostaglandins ineffective. Secretin (1-15 CU/kg iv) was without effect in both cats and guinea pigs. In guinea pigs, intravenous glucagon (120-360 micrograms.kg-1.h-1) or gastric inhibitory peptide (5 micrograms/kg) both increased HCO3(-) transport but not PD. Hence, prostaglandin-stimulated and hormone-stimulated mechanisms of HCO3(-) transport probably occur in mammalian duodenum as found previously in the isolated amphibian duodenum. The results suggest that epithelial HCO3(-) transport is a major mechanism of acid disposal, and thus mucosal protection, in mammalian duodenum under the control of hormones and endogenous prostaglandins.


Author(s):  
Yuanxu Jiang ◽  
Mingzhu Xia ◽  
Jing Xu ◽  
Qiang Huang ◽  
Zhongliang Dai ◽  
...  

AbstractDexmedetomidine (Dex), a highly selective α2-adrenergic receptor (α2AR) agonist, has an anti-inflammatory property and can alleviate pulmonary edema in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the mechanism is still unclear. In this study, we attempted to investigate the effect of Dex on alveolar epithelial sodium channel (ENaC) in the modulation of alveolar fluid clearance (AFC) and the underlying mechanism. Lipopolysaccharide (LPS) was used to induce acute lung injury (ALI) in rats and alveolar epithelial cell injury in A549 cells. In vivo, Dex markedly reduced pulmonary edema induced by LPS through promoting AFC, prevented LPS-induced downregulation of α-, β-, and γ-ENaC expression, attenuated inflammatory cell infiltration in lung tissue, reduced the concentrations of TNF-α, IL-1β, and IL-6, and increased concentrations of IL-10 in bronchoalveolar lavage fluid (BALF). In A549 cells stimulated with LPS, Dex attenuated LPS-mediated cell injury and the downregulation of α-, β-, and γ-ENaC expression. However, all of these effects were blocked by the PI3K inhibitor LY294002, suggesting that the protective role of Dex is PI3K-dependent. Additionally, Dex increased the expression of phosphorylated Akt and reduced the expression of Nedd4-2, while LY294002 reversed the effect of Dex in vivo and in vitro. Furthermore, insulin-like growth factor (IGF)-1, a PI3K agonists, promoted the expression of phosphorylated Akt and reduced the expression of Nedd4-2 in LPS-stimulated A549 cells, indicating that Dex worked through PI3K, and Akt and Nedd4-2 are downstream of PI3K. In conclusion, Dex alleviates pulmonary edema by suppressing inflammatory response in LPS-induced ALI, and the mechanism is partly related to the upregulation of ENaC expression via the PI3K/Akt/Nedd4-2 signaling pathway.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Paulina Smyk ◽  
Iga Hołyńska-Iwan ◽  
Dorota Olszewska-Słonina

Background. Propolis and its ethanol extract show positive germicidal, bacteriostatic, and anti-inflammatory antioxidants and regenerative properties after use on the surface of the skin. Propolis is in common use in production of cosmetics and in folk medicine. The influence of this resinous mixture on ion channels, channels located in skin cells membranes and skin electrical resistance, was not explained. Objective. The main aim of the study was the evaluation of electrophysiological skin parameters during mechanical and chemical-mechanical stimulation after use of ethanol extract of propolis and propolis ointment in comparison with iso-osmotic Ringer solution. Methods. Skin fragments were taken from white New Zealand rabbits and distributed into three experimental groups which were incubated in ethanol extract of propolis (EEP), propolis ointment, and Ringer solution. Then they were placed in a Ussing chamber to measure electrophysiological parameters values. Results. In this study the influence of EEP on changes in value of electrical potential during block of chloride ions transport at the same time was observed. Ethanol propolis extract dissolved in water increases the transepidermal sodium ions transport in contrast to propolis ointment. Conclusion. The way of preparation cosmetics, which contain propolis, has effects on transepidermal ions transport in the rabbit’s skin. The value of skin electrical resistance is changing with penetration depth of active propolis substances contained in cosmetics.


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