The role of endothelin ET(B) receptor-mediated action in the development and maintenance of deoxycorticosterone acetate (DOCA)-salt-induced hypertension was evaluated using the spotting-lethal (sl) rat which carries a naturally occurring deletion in the ET(B) receptor gene. Homozygous (sl/sl) rats treated with DOCA-salt for 1 week exhibited an earlier onset of hypertension than heterozygous (sl/+) and wild-type (+/+) rats (systolic blood pressure, SEP; 156.7 ± 3.4 versus 128.8 ± 5.3 and 132.9 ± 3.7 mmHg, respectively). Four weeks after the start of DOCA-salt treatment, homozygous rats developed marked hypertension, with a SBP of 206.0 ± 4.5 mmHg, compared with 184.8 ± 10.7 mmHg in heterozygous and 164.3 ± 4.8 mmHg in wild-type rats. Cardiovascular hypertrophy and renal dysfunction observed after 6 weeks treatment with DOCA-salt were more severe in homozygous rats, compared to wild-type and heterozygous animals. These evidences support strongly the view that ET(B) receptor-mediated actions are a protective factor in the pathogenesis of DOCA-salt-induced hypertension.
- Deoxycorticosterone acetate-salt hypertension
- ET(B) receptor
- Renal function
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