Alveolar liquid clearance in the anesthetized ventilated guinea pig

Abstract

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.

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

“…Previous studies (17,34,35) demonstrated that before birth, preterm amiloride sensitivity is close to 100% because there seem to exist few or no other pathways for Na ϩ absorption. During normal lung development, amiloride does not affect lung fluid secretion at 61 days gestation.…”

“…The other four guinea pigs remained anesthetized until the 1-h experimental time had passed and were then killed, and samples were obtained. At this time, a blood sample was obtained for FD70 analysis, and the lungs were collected for determination of extravascular plasma equivalents as previously described (31,34,40,46). Trichloroacetic acid (TCA) precipitation of plasma and urine samples verified that the FITC label (Ͼ97%) remained bound to the dextran tracer throughout the experimental time period.…”

“…Passage of FD70 molecules across the endothelial-epithelial barriers was considered to be equal to that of albumin, since they have similar molecular masses (70 vs. 68 kDa). The theory and method behind the plasma equivalent determination have been described in multiple published reports and in various animal species (31,34,40,46). We calculated endothelial protein leak using the FD70 concentrations in the different compartments and applying them in the equation:…”

“…Amiloride at a concentration of 1 mM was used because a large fraction becomes protein bound and a significant fraction rapidly leaves the air spaces due to its low molecular weight (37,49); therefore, the active alveolar concentration was likely lower. This amiloride concentration has been used in earlier studies (17,34,48).…”

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

“…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.…”