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-1H-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 +/- 9 mmHg). 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.