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Enhanced blood pressure sensitivity to DOCA‐salt treatment in endothelin ET B receptor‐deficient rats
Author(s) -
Matsumura Yasuo,
Kuro Toshihiko,
Konishi Fumiko,
Takaoka Masanori,
Gariepy Cheryl E,
Yanagisawa Masashi
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703157
Subject(s) - medicine , endocrinology , endothelin receptor , blood pressure , receptor , endothelin 1 , pathogenesis , chemistry
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, 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 ET B 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