Regulatory effects of aerosolized budesonide and adrenalectomy on the lung content of endothelin-1 in the rat.
This study was designed to investigate the effect of inflammation and glucocorticosteroids (GCS) on the content of endothelin-1-like immunoreactivity (ET-LI) in the rat lung. Following intratracheal instillation of Sephadex beads, which induces a long-lasting inflammation in the lung, there was an increase in the lung content of ET-LI measured by RIA. This increase was abolished by locally administered aerosolized budesonide at doses that had only minor systemic effects (measured as a reduction in body weight). In a second series of experiments, rats were subjected to surgical adrenalectomy in order to reduce the levels of endogenous GCS. This procedure elevated the ET-LI levels in the lungs. In contrast, neither adrenalectomy nor high doses of budesonide administered systemically affected the concentration of ET-LI in the kidney. It is concluded that the lung ET levels are elevated in inflammatory conditions and that this increase is highly sensitive to locally administered GCS. Endogenous GCS may, directly or indirectly, play a role in the regulation of lung ET content but there seems to be no general GCS effect on basal tissue levels of ET.
Andersson
S E
SE
Department of Pharmacology 1 and 2, Astra-Draco AB, Lund, Sweden.
Eirefelt
S
S
Zackrisson
C
C
Hemsén
A
A
Dahlbäck
M
M
Lundberg
J M
JM
D000280:Administration, Inhalation; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019819:Budesonide; D002851:Chromatography, High Pressure Liquid; D016232:Endothelins / Q000187:drug effects / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001993:Bronchodilator Agents; D016232:Endothelins; D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide