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Functional Roles of Endothelin ETB Receptor in the Vascular Disease and Its Sex Difference

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Author(s): Kento Kitada | Mamoru Ohkita | Yasuo Matsumura

Journal: Molecular and Cellular Pharmacology
ISSN 1938-1247

Volume: 3;
Issue: 2;
Start page: 45;
Date: 2011;
Original page

Keywords: Endothelin | Endothelin Receptor | Vascular Disease | Sex Difference | Neointimal Formation | Estrogen

ABSTRACT
Increasing evidence suggests that ET-1/ET receptor system plays an important role in the pathogenesis and development of vascular diseases. However, the functional roles of ETB receptor have not been fully elucidated while there are great hopes that ET receptor antagonists are effective for the treatment of vascular diseases. Thus, it has no definitive answer which type of ET receptor antagonist is the most preferable to prevent the vascular diseases. Our recent study has indicated that the antagonism of ETA receptor system is essential for preventing the vascular remodeling irrespective of the presence of the ETB receptor-mediated action, although the selective inhibition of ETB receptor system causes harmful effect in the development of neointimal formation after the vascular injury. On the other hand, the involvement of ET system in sex difference of cardiovascular diseases has attracted attention recently. We demonstrated that the sex differences in the vascular injury-induced neointimal formation are abolished in ETB receptor-inhibited condition. The lack of vasoprotective effects of estrogen and the augmentation of ETA receptor-mediated actions may be responsible for the abolition of this sex differences. These findings suggest that ETB receptor system is involved in the sex differences of vascular diseases and that the efficacious treatment of ET receptor antagonist for vascular disease differs between sexes.
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