Lung-liquid production in vitro by lungs from fetal guinea pigs: effects of amiloride on responses to aldosterone

Abstract

Lungs from near-term fetal guinea pigs (62 ± 2 days of gestation) were supported in vitro for 3 h; lung-liquid production was monitored by a dye-dilution method based on Blue Dextran 2000. Untreated preparations produced fluid at 1.26 ± 0.14 mL∙kg−1 body mass∙h−1, with no significant change over the ensuing hours (ANOVA, regression analysis; n = 16). Experimental preparations received aldosterone at plasma concentrations reported to be present at birth. Aldosterone produced rapid, significant reductions in fluid production, and occasionally reabsorptions, which persisted beyond treatment. Reductions during treatment were as follows: 10−8 M aldosterone, 90.8 ± 4.9% (P < 0.001; n = 4); 2 × 10−9 M aldosterone, 64.1 ± 16.6% (P < 0.05–0.001; n = 6), and 7 × 10−10 M aldosterone, 48.6 ± 11.7% (P < 0.005–0.001; n = 6). The linear log dose response curve (r = 0.99) showed a theoretical threshold at 3.4 × 10−11 M aldosterone. Responses to 7 × 10−10 M aldosterone were abolished by 10−6 M amiloride. At the highest concentration of aldosterone (10−8 M), 10−6 M amiloride significantly reduced responses, and the changes were no longer significant by ANOVA. At both high and low aldosterone concentrations, responses with amiloride were significantly lower than those without amiloride (ANOVA, P < 0.03–0.04). Amiloride controls and untreated preparations showed no significant changes in fluid production. It is concluded that aldosterone at plasma concentrations present at birth can cause reductions in lung-liquid production or reabsorption through effects on amiloride-sensitive Na+ channels, and that the responses are remarkably rapid.