Liquid flow across the epithelium of the artificially perfused lung of fetal and postnatal sheep.

Abstract

SUMMARY1. The lungs of five fetal (133-140 days gestation) and thirty-four postnatal (2-240 days) sheep were artificially perfused in situ with warmed and oxygenated sheep blood. In postnatal animals the airspace of the lung was filled with liquid similar in composition to fetal lung liquid. In fetal and postnatal animals luminal liquid volume was measured by the impermeant tracer technique.2. Under resting conditions the pulmonary epithelium of fetal animals secreted liquid at a mean (±s.E.M.) rate of 2-0 (±0 4) ml (kg body weight)-' h-', those of postnantal animals absorbed liquid at -1-8 (±0 2) ml (kg body weight)-' h-1.3. Addition of 2,4-dinitrophenol to achieve a concentration of 1P5 x 10-3 M in the perfusing blood in postnatal animals caused complete cessation of liquid absorption. 4. Light and electron microscopic examination of the lung after periods of up to 6 h of artificial perfusion showed no evidence of epithelial damage. From 3 h onwards, liquid accumulation was evident in the perivascular spaces.5. Addition of adrenaline to the perfusate in fetal animals caused absorption of liquid to occur at a mean rate of -29 (± 1P3) ml (kg body weight)-' h-1. In postnatal animals adrenaline caused the rate of liquid absorption to increase from a mean rate of -14 (± 0 2) to -2-2 (± 0 3) ml (kg body weight)-' h-1.6. In the fetus addition of amiloride (0-8 x 10-4 M) to the luminal fluid blocked adrenaline-induced liquid absorption and caused secretion to occur at 1-3 (±0 3) ml (kg body weight)-' h-1.7. In postnatal animals the response to amiloride was age dependent. In newborn lambs (2-14 days) amiloride blocked liquid absorption and caused secretion of liquid to occur in seven out of eight animals at a mean rate of 09 (±03) ml (kg body weight)-' h-' (n = 8). In older animals (15-240 days) the characteristic response to amiloride was slowing of the rate of liquid absorption (mean rate of absorption, -0-2 (±0 09) ml (kg body weight)-' h-1, n = 18) with liquid secretion being seen in only three of eighteen animals.8. We conclude firstly that the mechanisms that mediate secretion of liquid by the fetal pulmonary epithelium appear to be retained in the lung for at least the first 14 days of postnatal life and secondly that the mechanisms which underlie absorption MS 9203 C. A. RAMSDEN AND OTHERS of liquid change during postnatal development with the progressive acquisition of an absorptive process that cannot be blocked by amiloride.

Hydrogen sulfide decreases β-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption

“…agents have long been known to stimulate absorption of luminal lung liquid in both the fetus (13,61,83) and the postnatal animal (11,69), and more recent reports show the same effect of terbutaline, i.e., stimulating amiloride-sensitive sodium absorption (9,89). It is well established that ␤-adrenergic receptor agonists increase the abundance of ENaCs in the apical membrane of pulmonary epithelial cells by a cAMP-dependent pathway (8,90).…”

Invited Review: Clearance of lung liquid during the perinatal period

“…The lung is absorptive at rest postnatally but can be induced to secrete in the artificially perfused neonatal lamb lung if Na ϩ absorption is blocked by addition of luminal amiloride (60). However, this response is lost after 2 wk of age.…”

Signalling

“…anaesthesia. Sheep lungs were artificially perfused in situ with warmed oxygenated sheep blood, as described in Ramsden et al (1992).…”