Enhanced blood pressure sensitivity to DOCA‐salt treatment in endothelin ETB receptor‐deficient rats

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 treated with DOCA‐salt for 1 week exhibited an earlier onset of hypertension than heterozygous (sl/+) and wild‐type (+/+) rats (systolic blood pressure, SBP; 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 4‐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 ETB receptor‐mediated actions are a protective factor in the pathogenesis of DOCA‐salt‐induced hypertension. British Journal of Pharmacology (2000) 129, 1060–1062; doi:10.1038/sj.bjp.0703157