The role of endothelin ETB 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 ETB receptor gene. Homozygous (sl/sl) rats treat
ed with DOCA-salt for 1 week exhibited an earlier onset of hypertension tha
n heterozygous (sl/+) and wild-type (+/+) rats (systolic blood pressure, SB
P: 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 develo
ped marked hypertension. with a SBP of 206.0 +/- 4.5 mmHg, compared with 18
4.8 +/- 10.7 mmHg in heterozygous and 164.3 +/- 4.8 mmHg in wild-type rats.
Cardiovascular hypertrophy and renal dysfunction observed after 4-weeks tr
eatment with DOCA-salt were more severe in homozygous rats. compared to wil
d-type and heterozygous animals. These evidences support strongly the view
that ETB receptor-mediated actions are a protective factor in the pathogene
sis of DOCA-salt-induced hypertension.