Vasoprotective effects of an endothelin receptor antagonist in ovariectomized female rats.
OBJECTIVE
The effects of hormone replacement therapy with estrogen on cardiovascular disease in postmenopausal women are still controversial. In the present study, we examined the effects of an endothelin (ET) receptor antagonist (ERA) and/or angiotensin receptor blocker (ARB) on neointimal formation following vascular injury in ovariectomized (OVX) female rats.


METHODS
Female rats were divided into intact female and OVX groups. The right carotid artery was subjected to balloon injury, and harvested 2 weeks later.


RESULTS
In the intact female groups, treatment with ARB (L-158809; 1 mg/kg/day) for two weeks after the injury significantly decreased neointimal formation, whereas treatment with the ERA (J-104132; 10 mg/kg/day) did not affect neointimal formation. On the other hand, the ERA markedly decreased neointimal formation after the injury in the OVX groups; however, neointimal formation was not significantly improved by the ARB treatment. In addition, the combined treatment with 17β-estradiol (20 μg/kg/day) or the ERA and ARB markedly suppressed neointimal formation after the balloon injury in the OVX groups, whereas no combinational effects were observed due to the combined treatment with 17β-estradiol and the ERA.


CONCLUSIONS
These results suggest that ERAs have estrogen-like vasoprotective effects on neointimal formation following balloon injury in OVX rats. ERAs may be useful as an alternative therapy to prevent vascular disease in postmenopausal women.
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan; Department of Pharmacology, Kagawa University, Kagawa, Japan.
Kento
K
Kitada
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Nozomi
N
Yui
Department of Internal Medicine III, Osaka Medical College, Osaka, Japan.
Tatsuhiko
T
Mori
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Mamoru
M
Ohkita
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan. Electronic address: ymatumura@gly.oups.ac.jp.
Yasuo
Y
Matsumura
D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D009249:NADP / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy / Q000473:pathology; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D020011:Protective Agents; D013481:Superoxides; D004958:Estradiol; D009249:NADP
Angiotensin II; Balloon injury; Endothelin-1; Estrogen; Neointimal formation