Role of endogenous cortisol in basal liquid clearance from distal air spaces in adult guinea-pigs.
1. 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-beta-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. 2. 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%). 3. 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 alpha-subunit (alphaENaC) mRNA in lung tissue was decreased after 2 days of metyrapone pretreatment and after 7 days pretreatment or after co-injection with dexamethasone, alphaENaC mRNA expression was restored towards control levels. 4. 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.
Norlin
A
A
Department of Animal Physiology, Lund University, Helgonavägen 3B, S-223 62 Lund, Sweden. andreas.norlin@zoofys.lu.se
Baines
D L
DL
Folkesson
H G
HG
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003907:Dexamethasone / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D053503:Epithelial Sodium Channels; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate; D006854:Hydrocortisone / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects; D015222:Sodium Channels / Q000235:genetics
D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D000584:Amiloride; D003907:Dexamethasone; D006854:Hydrocortisone; D004640:Emetine; D008797:Metyrapone