Increased susceptibility to deoxycorticosterone acetate-salt-induced hyper-tension in endothelin-B-receptor-deficient rats

Citation
Y. Matsumura et al., Increased susceptibility to deoxycorticosterone acetate-salt-induced hyper-tension in endothelin-B-receptor-deficient rats, J CARDIO PH, 36, 2000, pp. S86-S89
Citations number
13
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
ISSN journal
0160-2446 → ACNP
Volume
36
Year of publication
2000
Supplement
1
Pages
S86 - S89
Database
ISI
SICI code
0160-2446(2000)36:<S86:ISTDAH>2.0.ZU;2-R
Abstract
We evaluated the role of endothelin-B- (ETB) receptor-mediated action in th e development and maintenance of deoxycorticosterone acetate (DOCA)-salt-in duced hypertension, cardiovascular hypertrophy and renal damage, using the spotting lethal (sl) rat which carries a naturally occurring deletion in th e ETB-receptor gene. Homozygous (sl/sl) rats exhibit abnormal development o f the neural crest-derived epidermal melanocytes and the enteric nervous sy stem (ENS), and do not live beyond 1 month because of intestinal agangliono sis and resulting intestinal obstruction. Therefore, the dopamine-beta -hyd roxylase (D betaH) promoter was used to direct ETB transgene expression in sl/sl rats to support normal ENS development. D betaH-ETB sl/sl rats live i nto adulthood and are healthy, expressing ETB-receptor in adrenals and othe r adrenergic neurons. When homozygous (sl/sl) and wild-type (WT) (+/+) rats , all of which were transgenic, were treated with DOCA and salt for 4 weeks , the homozygous rats exhibited significantly earlier and higher increases in systolic blood pressure than WT rats. The daily oral administration of A BT-627, a selective ETA-receptor antagonist, almost completely suppressed t he DOCA-salt-induced hypertension in both groups. Renal dysfunction and his tological damage induced by DOCA-salt treatment were more severe in homozyg ous than in WT rats. Increased and marked vascular hypertrophy of the aorta was also observed in homozygous rats, compared with WT rats. Renal and vas cular injuries induced by DOCA and salt were significantly improved by ABT- 627 administration. We propose that ETB-receptor-mediated actions are prote ctive factors in the pathogenesis of DOCA-salt-induced hypertension. ETA-me diated actions are at least partly responsible for the increased susceptibi lity to DOCA-salt-induced hypertension and related tissue injuries in ETB-r eceptor-deficient rats.