Chronic urotensin II receptor antagonist treatment does not alter hypertrophy or fibrosis in a rat model of pressure-overload hypertrophy
Andrew R Kompa, Bing H Wang, Arintaya Phrommintikul, Pei Y Ho, Darren J Kelly, David J Behm, Stephen A Douglas, Henry Krum
PEPTIDES | ELSEVIER SCIENCE INC | Published : 2010
Urotensin II (UII) is a potential mediator in the pathogenesis of cardiovascular disease, and inhibition of its actions at the urotensin receptor (UT) has been shown to improve cardiac function and structural changes of the myocardium in a model of myocardial infarction. In this study we utilized a model of pressure-overload hypertrophy induced by abdominal aortic constriction (AAC) which resulted in hypertrophy, increased fibrosis and impaired diastolic and systolic function. These changes were associated with a 4-fold increase in UII protein expression in the myocardium. Treatment of animals with a selective UT (SB-657510) antagonist for 20 weeks at a dose of 1500 ppm did not improve cardi..View full abstract
Awarded by National Health and Medical Research Council of Australia
This study was supported by GlaxoSmithKline and National Health and Medical Research Council of Australia grants  and . The authors would also like to thank GSK for the gift of compound SB-657510, Dr. Chris Evans (GSK) for measurement of plasma levels of SB-657510, and Ms. Mariana Pacheco, Ms. Jemma Court and Ms. Gordana Kel for technical support with the animal studies.