| Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. | |
| | |
MedLine Citation:
|
PMID: 21816148 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The pharmacological profile of a novel angiotensin II type 1 receptor blocker, azilsartan medoxomil, was compared with that of the potent angiotensin II receptor blocker olmesartan medoxomil. Azilsartan, the active metabolite of azilsartan medoxomil, inhibited the binding of [(125)I]-Sar(1)-I1e(8)-angiotensin II to angiotensin II type 1 receptors. Azilsartan medoxomil inhibited angiotensin II-induced pressor responses in rats, and its inhibitory effects lasted 24h after oral administration. The inhibitory effects of olmesartan medoxomil disappeared within 24h. ID(50) values were 0.12 and 0.55mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In conscious spontaneously hypertensive rats (SHRs), oral administration of 0.1-1mg/kg azilsartan medoxomil significantly reduced blood pressure at all doses even 24h after dosing. Oral administration of 0.1-3mg/kg olmesartan medoxomil also reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In renal hypertensive dogs, oral administration of 0.1-1mg/kg azilsartan medoxomil reduced blood pressure more potently and persistently than that of 0.3-3mg/kg olmesartan medoxomil. In a 2-week study in SHRs, azilsartan medoxomil showed more stable antihypertensive effects than olmesartan medoxomil and improved the glucose infusion rate, an indicator of insulin sensitivity, more potently (≥10 times) than olmesartan medoxomil. Azilsartan medoxomil also exerted more potent antiproteinuric effects than olmesartan medoxomil in Wistar fatty rats. These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent. |
| | |
Authors:
|
Keiji Kusumoto; Hideki Igata; Mami Ojima; Ayako Tsuboi; Mitsuaki Imanishi; Fuminari Yamaguchi; Hiroki Sakamoto; Takanobu Kuroita; Naohiro Kawaguchi; Nobuhiro Nishigaki; Hideaki Nagaya |
Related Documents
:
|
9472908 - Relation of blood volume and blood pressure in orthostatic intolerance. 9429658 - Decreased capacitance response with age in lower limbs of humans--a potential error in ... 7949808 - Circulatory responses in children with unexplained syncope evaluated by continuous non-... 9868708 - Paradoxical hypotension during dobutamine infusion for myocardial perfusion scintigraphy. 6051778 - Observations on the rhythmic variation in the cat carotid body chemoreceptor activity w... 3397698 - The effect of variations of ventricular volume on the electrocardiogram. a comparison o... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-7-28 |
Journal Detail:
|
Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-8-5 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
|
Metabolic Disease Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Osaka, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Both ?(2B)- and ?(2C)-adrenoceptor subtypes are involved in the mediation of centrally induced gastr...
Next Document: Assessment of research models for testing gene-environment interactions.