+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



European Journal of Pharmacology 669(1-3): 84-93



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 0.55 mg/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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036164087

Download citation: RISBibTeXText

PMID: 21816148

DOI: 10.1016/j.ejphar.2011.07.014


Related references

Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril. Journal of Human Hypertension 27(8): 479-486, 2013

The Novel Angiotensin II Receptor Blocker Azilsartan Medoxomil Ameliorates Insulin Resistance Induced by Chronic Angiotensin II Treatment in Rat Skeletal Muscle. Cardiorenal Medicine 3(2): 154-164, 2013

Azilsartan medoxomil: a new Angiotensin receptor blocker. Clinical Therapeutics 33(11): 1577-1589, 2012

Azilsartan Medoxomil (Edarbi): The Eighth Angiotensin II Receptor Blocker. P and T 36(10): 634-640, 2012

Azilsartan Medoxomil Angiotensin Receptor Blocker in the Treatment of Hypertension. 2013

Azilsartan medoxomil in the treatment of hypertension: the definitive angiotensin receptor blocker?. Expert Opinion on PharmacoTherapy 14(16): 2249-2261, 2014

Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension 57(3): 413-420, 2011

The angiotensin receptor blocker, azilsartan medoxomil (TAK-491), suppresses vascular wall expression of plasminogen activator inhibitor type-I protein potentially facilitating the stabilization of atherosclerotic plaques. Journal of Cardiovascular Pharmacology 58(2): 143-148, 2011

Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African-American patients with hypertension. Journal of Clinical Hypertension 19(7): 695-701, 2017

Patients With Newly Diagnosed Hypertension Treated With the Renin Angiotensin Receptor Blocker Azilsartan Medoxomil vs Angiotensin-Converting Enzyme Inhibitors: The Prospective EARLY Registry. Journal of Clinical Hypertension 17(12): 947-953, 2016

Efficacy and safety of azilsartan medoxomil, an angiotensin receptor blocker, in Korean patients with essential hypertension. Clinical Hypertension 24: 2, 2018

Mps 03-04 Efficacy And Safety Of The Novel Angiotensin Receptor Blocker, Azilsartan-Medoxomil, In Korean Patients With Essential Hypertension. Journal of Hypertension 34: e84-e85, 2016

Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. Journal of Clinical Hypertension 13(7): 467-472, 2012

The renin-angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril in clinical trials versus routine practice: insights from the prospective EARLY registry. Trials 16: 581, 2016

Additive antihypertensive and antihypertrophic effects of long-acting Ca blockers in uncontrolled hypertensive patients with angiotensin-receptor blocker based treatment. International Heart Journal 50(5): 555-570, 2009