Hypertension, Vol 23, 288-293, Copyright © 1994 by American Heart Association
K Hasegawa, H Fujiwara, K Doyama, T Inada, S Ohtani, T Fujiwara, K Hosoda, K Nakao and S Sasayama
Endothelin-1 is a potent vasoconstrictor produced by vascular endothelial
cells. A recently cloned endothelin-1-selective receptor, the endothelin-A
receptor, mediates the vasoconstrictive action of endothelin-1. Because
endothelin-1 also possesses mitogenic properties, it may play a role in
regulating the proliferation of intimal smooth muscle cells. In this study,
we analyzed the expression of endothelin-A receptor gene in the thickened
arterial intima of patients with hypertension. Internal mammary artery
specimens obtained from 12 patients undergoing cardiovascular surgery were
subjected to in situ hybridization using a digoxigenin-labeled cRNA probe.
High, homogeneous signals of endothelin-A receptor mRNA were observed in
the medial smooth muscle cells of all vessels examined but not in the
endothelial cells. Patients with hypertension displayed more severe intimal
thickening than those without hypertension. Immunohistochemical analysis
suggested that almost all of the intimal proliferative cells originated
from smooth muscle cells. In contrast to media, endothelin-A receptor mRNA
signals in intimal smooth muscle cells were low and heterogeneous. In the
thickened arterial intima of hypertensive patients, the signals were
detected just beneath the luminal endothelium but not deep in the intimal
smooth muscle cell layer. By contrast, staining with anti-alpha-smooth
muscle actin antibody was more intense in the deep layer than in the
subendothelium. These findings suggest that the modulation of endothelin-A
receptor gene expression in smooth muscle cells differs between the intima
and media. Its regulated expression in intimal smooth muscle cells might
affect the proliferative activity of these cells in patients with
hypertension.
ARTICLES
Endothelin-1-selective receptor in the arterial intima of patients with hypertension
Third Division, Faculty of Medicine, Kyoto University, Japan.
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