Hemodynamic and biochemical effects of endothelin-A- and -B- receptor antagonist TAK-044 in stroke-prone spontaneously hypertensive rats

Citation
M. Naruse et al., Hemodynamic and biochemical effects of endothelin-A- and -B- receptor antagonist TAK-044 in stroke-prone spontaneously hypertensive rats, J CARDIO PH, 36, 2000, pp. S334-S336
Citations number
13
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
ISSN journal
01602446 → ACNP
Volume
36
Year of publication
2000
Supplement
1
Pages
S334 - S336
Database
ISI
SICI code
0160-2446(2000)36:<S334:HABEOE>2.0.ZU;2-2
Abstract
We have demonstrated previously that endothelin-l (ET-1) mRNA expression is increased in hypertensive rats. The aim of the study reported hers was to elucidate the effects of the endothelin (ET) receptor antagonist on the hem odynamic and biochemical parameters in stroke-prone spontaneously hypertens ive rats (SHRSPs/Izm). The endothelin-A- and -B- (ETA/ETB) receptor antagon ist (TAK-044, Takeda Chemical Industries, Osaka, Japan) was administered su bcutaneously at a dose of 10 mg/kg/day from the age of 8 weeks for 4 weeks. Blood samples and tissues of the kidney, heart and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by rever se transcriptase-polymerase chain reaction (RT-FCR) followed by Southern bl ot analysis. Treatment with TAK-044 resulted in a significant decrease in s ystolic blood pressure (SBP), blood urea nitrogen (BUN), serum creatinine c oncentration, plasma aldosterone level, heart weight, and kidney weight. In addition, ET-1 contents and mRNA expression level in the kidney, heart and brain were significantly decreased by the treatment with TAK-044. These re sults suggest that the ET receptor antagonist TAK-034 is able to attenuate ET-1 gene expression in addition to its specific antagonism of the biologic al actions of ET via the receptors.