التفاصيل البيبلوغرافية
| العنوان: |
The orally active urotensin receptor antagonist, KR36676, attenuates cellular and cardiac hypertrophy |
| المؤلفون: |
Oh, K S, Lee, J H, Yi, K Y, Lim, C J, Lee, S, Park, C H, Seo, H W, Lee, B H |
| المساهمون: |
National Research Foundation, Republic of Korea |
| المصدر: |
British Journal of Pharmacology ; volume 172, issue 10, page 2618-2633 ; ISSN 0007-1188 1476-5381 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2015 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Background and Purpose Blockade of the actions of urotensin‐ II ( U ‐ II ) mediated by the urotensin ( UT ) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT receptor antagonist, 2‐(6,7‐dichloro‐3‐oxo‐2 H ‐benzo[b][1,4]oxazin‐4(3 H )‐yl)‐ N ‐methyl‐ N ‐(2‐(pyrrolidin‐1‐yl)‐1‐(4‐(thiophen‐3‐yl)phenyl) ethyl)acetamide ( KR 36676). Experimental Approach Pharmacological properties of KR 36676 were studied in a range of in vitro assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by transverse aortic constriction ( TAC ) or myocardial infarction ( MI ). Key Results KR 36676 displayed high binding affinity for the UT receptor ( K i : 0.7 nM), similar to that of U ‐ II (0.4 nM), and was a potent antagonist at that receptor ( IC 50 : 4.0 nM). U ‐ II ‐induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR 36676 (≥0.01 μM). Oral administration of KR 36676 (30 mg·kg −1 ) in a TAC model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR 36676 restored cardiac function and myocyte size in rats with MI ‐induced cardiac hypertrophy. Conclusions and Implications A highly potent UT receptor antagonist exerted anti‐hypertrophic effects not only in infarcted rat hearts but also in pressure‐overloaded mouse hearts. KR 36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U ‐ II and UT receptors in cardiac hypertrophy. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1111/bph.13082 |
| الإتاحة: |
https://doi.org/10.1111/bph.13082Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.6250CE8A |
| قاعدة البيانات: |
BASE |
