Role of endogenous cortisol in basal liquid clearance from distal air spaces in adult guinea‐pigs

Abstract

We investigated the role of endogenous cortisol in the modulation of distal air space liquid clearance in adult guinea-pigs. Cortisol synthesis was inhibited with the 11-β-hydroxylase inhibitor metyrapone (0–7 days pretreatment). After cortisol synthesis inhibition, distal air space liquid clearance was measured by the increase in concentration of an instilled 5 % albumin solution after 1 h. Two days of metyrapone pretreatment resulted in a 46 ± 19 % decrease in plasma cortisol levels compared with control, which was paralleled by a 60 ± 13 % decrease in distal air space liquid clearance. The Na+ channel inhibitor amiloride inhibited 40 ± 22 % of distal air space liquid clearance in control animals but did not inhibit distal air space liquid clearance in the metyrapone-pretreated group. Co-injection of dexamethasone prevented the inhibition by metyrapone and the amiloride sensitivity of distal air space liquid clearance was greater than in control animals. After 7 days of metyrapone pretreatment, plasma cortisol levels and distal air space liquid clearance were not significantly different from normal, but amiloride sensitivity was greater than in control animals (91 ± 37 %). Pretreatment with emetine, a protein synthesis inhibitor, reduced distal air space liquid clearance in control animals and in dexamethasone-co-injected animals, but failed to inhibit distal air space liquid clearance after metyrapone pretreatment. Expression of the epithelial sodium channel α-subunit (αENaC) mRNA in lung tissue was decreased after 2 days of metyrapone pretreatment and after 7 days pretreatment or after co-injection with dexamethasone, αENaC mRNA expression was restored towards control levels. Thus, endogenous cortisol is important for maintaining normal liquid balance in the adult guinea-pig lung and a critical regulatory pathway is by modulation of ENaC expression and/or function.