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

Matsumura, Y Kuro, T Konishi, F Takaoka, M Gariepy, CE Yanagisawa, M

Y. Matsumura et al., Enhanced blood pressure sensitivity to DOCA-salt treatment in endothelin ETB receptor-deficient rats, BR J PHARM, 129(6), 2000, pp. 1060-1062

15

INGLESE

Article

Pharmacology & Toxicology

BRITISH JOURNAL OF PHARMACOLOGY

0007-1188 → ACNP

129

6

2000

1060 - 1062

ISI

0007-1188(200003)129:6<1060:EBPSTD>2.0.ZU;2-V

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.