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Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery

Dept of Respiratory Medicine, Juntendo University, School of Medicine, Tokyo, Japan

CORRESPONDENCE: H. Takahashi, Clinic, Personnel Division, Mitsui & Co, Ltd, 1-2-1 Otemachi, Chiyoda-Ku, Tokyo, 100-0004,, Japan. Fax: 81 332859152

Keywords: endothelial cell, endothelin converting enzyme, hypoxic pulmonary hypertension, smooth muscle cell

Received: August 28, 2000
Accepted March 2, 2001

Since pulmonary vasculature is complex in terms of regional difference in structure and function, it is important to understand the site of endothelin (ET) synthesis and the distribution of the ET system along the axial pathways of pulmonary artery.

The expression of big ET-1, ET converting enzyme (ECE) and ET_A receptors were examined in rat pulmonary arteries under normal and hypoxic conditions using an immunohistochemical method and Northern blot analysis.

In normal conditions, big ET-1 was expressed in the intima and media of pulmonary arteries with a predominant distribution in the distal segments and a preferential localization in the media, while ET_A receptors were dominantly expressed in the proximal segments. ECE was constitutively expressed in the intima and media. Following exposure to hypoxia, messenger ribonucleic acid (mRNA) expression of ET-1 and ET_A receptors were up-regulated by two-fold and immunoreactivities for big ET-1, ECE, and ET_A receptors significantly increased by two to five-fold in the distal segments.

Smooth muscle cells are an important source of endothelin-1 in the pulmonary artery. The distribution of big endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in normal conditions while their expression concomitantly increased in the distal segments in hypoxic conditions. This heterogeneity may play an important role in the regulation of pulmonary vascular tone.

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