Fluid absorption by rat lung in situ: pathways for sodium entry in the luminal membrane of alveolar epithelium.

Abstract

SUMMARY1. The purpose of the investigation was to characterize the luminal membrane and the paracellular pathway of rat lung alveolar epithelium. Experiments were performed on lungs in situ instilled with isotonic, buffered Ringer solution and perfused with blood from a donor rat using cross-circulation technique.2. The rate of active Na+ transport was 4-4 pmol/(cm2 s). The fluid absorption was 156 nl/s, and was unaffected by the presence of protein in the instillate (166 nl/s). In the absence of Na+, fluid absorption was zero. Amiloride (10-3 M) reduced fluid absorption by 60 %. Amiloride, combined with absence of D-glucose, arrested fluid absorption completely. Phloridzin at the luminal side reduced fluid absorption whilst phloretin had no effect. Amiloride together with phloridzin (10-3 M) also arrested absorption. Thus, there are two entry systems for Na+ in the luminal membrane: Na+ channels and a Na+-D-glucose symport. These results show that alveolar fluid absorption is due to cellular activity. 4. Passive unidirectional flux of Na+, determined with 22Na+, was 9-9 pmol/(cm2 s) and that of Cl-, determined with 36C1-, was 12-4 pmol/(cm2 s). These fluxes were based on an assumed alveolar surface area of 5000 cm2. Transference numbers calculated from these figures are close to those in free solution, suggesting a neutral or weakly charged intercellular junctional pathway. The D-mannitol permeability in the paracellular pathway was 1-7 x 10-8 cm/s.5. It is a consequence of the proposed mechanism for fluid absorption that it becomes inoperative if the normally high reflexion coefficients for Na+ and Cl-are lowered in pathological states. In such conditions pulmonary oedema may develop depending on the net balance of passive mechanical and colloid-osmotic forces.6. An explanation ofthe reversal of fluid transport at the time of birth is presented.

Developmental changes in water permeability across the alveolar barrier in perinatal rabbit lung.

“…The initial rates of fluorescence increase are shown by the dashed lines in each curve. Note the slower initial rates in lungs at FD31 and just after birth (1 and 4 h) compared to lungs from older rabbits (12,36, and 60 h). By 120 h after birth, the initial rate of fluorescence increase was decreased.…”

“…By 12 h after birth, 80% of perinatal lung liquid is cleared (8)(9)(10). The ability to osmotically reabsorb fluid from the airspaces is retained throughout adult life (11)(12)(13).…”

Oxytocin-induced labor augments IL-1β-stimulated lung fluid absorption in fetal guinea pig lungs

“…All of this prepared the lungs for labor induction, having an additive stimulatory effect on lung fluid absorption after IL-1␤ stimulation and preterm delivery. It has also been demonstrated (3,5,6,19,31) that lung fluid is reabsorbed secondary to Na ϩ absorption and that this Na ϩ transport can be stimulated by agonist binding to ␤-adrenoceptors. Consequently, more ␤-adrenoceptors and higher ␤-adrenoceptor stimulation may lead to increased Na ϩ and fluid transport.…”

“…IL-1␣ also improved postnatal lung function with increased surfactant pool size without eliciting systemic inflammatory responses in lambs (14, 47). We recently reported that IL-1␤ pretreatment of timed-pregnant guinea pigs induced fluid absorption in fetal lungs, sodium transporter protein, and ␤-adrenoceptor expression via hypothalamus-pituitary-adrenal gland axis stimulation (48).Lung fluid absorption occurs secondarily to transepithelial Na ϩ absorption (3,5,8,17,22,31,35,37,45,48,49) and is driven by basolateral Na-K-ATPases (16, 23) and apical epithelial sodium channels (19,22,30,31). Fluid absorption occurs in near-term lungs (6,17,35,37,45) and is induced/ stimulated by cortisol and triiodothyronine (2, 20, 48) and labor-released epinephrine (17,35,45).…”

Gene regulation in the adaptive process to hypoxia in lung epithelial cells

“…During acute respiratory distress syndrome or at high altitude, alveoli flood with edema, thus impairing gas exchange (33). Active sodium transport is the primary mechanism responsible for removal of fluid from the distal air spaces (3). Overall, the process of transepithelial sodium transport can be considered a two-step process.…”