THE LUNG CONTENTS OF ENDOTHELIN ARE ALTERED BY THYROID-HORMONE STATUS IN RAT

Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium of cultured porcine endothelial cells and is widely distributed throughout the body, with relatively high levels in the kidney and lung. Animal studies have revealed that the lung appears to have the largest capacity for ET-1 removal from the blood stream. In this study we have examined the possible influence of thyroid status on immunoreactive endothelin (IR-ET) levels in the plasma and lung of the male rats. 3 weeks after the surgical removal of the thyroid gland from male rats, the IR-ET levels in the lung were reduced by 39%. Similarly, IR-ET levels were decreased 46% in the lung of rats rendered hypothyroid by treatment with 0.1% (w/w) PTU in the drinking water for 30 days, and replacement with daily L-thyroxine (T4) injections (5 mug/100 g) prevented this decrease. However, thyrotoxicosis induced by daily L-T4 injections (10 mug/100 g) also caused a decrease of the lung IR-ET levels by 49%. Nevertheless, the plasma IR-ET levels are similar in each group. Fast protein liquid chromatography study verified the presence of ET-1 immunoreactivity in both rat plasma and lung tissue extracts. This study demonstrates that euthyroid status is required for the maintenance of physiological concentrations of IR-ET in the lung of male rats.