Effects of the Endothelin ETA-Receptor Antagonist FR 139317 on Development of Hypertension and Cardiovascular Hypertrophy in Deoxycorticosterone Acetate-Salt Hypertensive Rats

The Japanese Journal of Pharmacology

Katsuya Fujita¹  Yohko Miyazaki¹  Masanori Takaoka¹  Shiro Morimoto¹  Yasuo Matsumura¹ 

[1] Department of Pharmacology, Osaka University of Pharmaceutical Sciences

关键词: Endothelin-1;    Endothelin ETA receptor;    FR139317;    Deoxycorticosterone acetate (DOCA)-salt hypertension;    Cardiovascular hypertrophy;   

DOI  :  10.1254/jjp.70.313

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(11)We investigated the role of endothelin-1 (ET-1) in the development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Two weeks after the start of DOCA-salt treatment, the rats were divided into two groups and were given FR139317 [(R)2[(R)-2-[(S)-2-[[ 1-(hexahydro-lH-azepinyl)]-carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl] amino-3-(2-pyridyl) propionic acid], a specific ETA-receptor antagonist, or its vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment served as controls. Vehicle-treated DOCA-salt rats developed marked hypertension after 4 weeks. FR139317 significantly suppressed the increase in systolic blood pressure with values averaging 163±8 mmHg (P < 0.05 vs DOCA-salt rats receiving vehicle, 195±9mmHg). Morphological studies in the rats given the vehicle showed vascular medial hypertrophy, with a significant increase in the wall area and wall-to-lumen ratio. A marked decrease in vascular wall hypertrophy was observed in the FR139317-treated DOCA-salt rats. The cardiac hypertrophy in DOCA-salt hypertensive rats was also significantly reduced by FR139317. Therefore, these results suggest that ET-1 plays an important role in the development of DOCA-salt hypertension presumably by stimulating the ETA receptor. In addition, we found that an ETA-receptor antagonist effectively reduced cardiovascular hypertrophy in the rats, so the cardiovascular hypertrophy noted in DOCA-salt hypertensive rats may be related to ET-1.

【 授权许可】

Unknown