scholarly journals Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors

1999 ◽  
Vol 126 (4) ◽  
pp. 1057-1065 ◽  
Author(s):  
P M L Vanderheyden ◽  
F L P Fierens ◽  
J P De Backer ◽  
N Fraeyman ◽  
G Vauquelin
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Receptor Antagonists ◽  
At1 Receptors ◽  
At1 Receptor Antagonists

scholarly journals Distinctions between non-peptide angiotensin II AT1-receptor antagonists

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S24-S31 ◽  
Author(s):  
Georges Vauquelin ◽  
Frederik LP Fierens ◽  
Ilse Verheijen ◽  
Patrick ML Vanderheyden
Keyword(s):  
Angiotensin Ii ◽  
Inositol Phosphate ◽  
At1 Receptor ◽  
Maximal Response ◽  
Ang Ii ◽  
Receptor Antagonists ◽  
Experimental Conditions ◽  
At1 Receptors ◽  
At1 Receptor Antagonists ◽  
Slow Dissociation

A far-reaching understanding of the molecular action mechanism of AT1-receptor antagonists (AIIAs) was obtained by using CHO cells expressing transfected human AT 1-receptors. In this model, direct [3H]-antagonist binding and inhibition of agonist-induced responses (inositol phosphate accumulation) can be measured under identical experimental conditions. Whereas preincubation with a surmountable AIIA (losartan) causes parallel shifts of the angiotensin II (Ang II) concentration-response curve, insurmountable antagonists also cause partial (i.e., 30% for irbesartan, 50% for valsartan, 70% for EXP3174,) to almost complete (95% for candesartan) reductions of the maximal response. The main conclusions are that all investigated antagonists are competitive with respect to Ang II. They bind to a common or overlapping site on the receptor in a mutually exclusive way. Insurmountable inhibition is related to the slow dissociation rate of the antagonist-receptor complex (t 1/2 of 7 minutes for irbesartan, 17 minutes for valsartan, 30 minutes for EXP3174 and 120 minutes for candesartan). Antagonist-bound AT1-receptors can adopt a fast and a slow reversible state. This is responsible for the partial nature of the insurmountable inhibition. The long-lasting effect of candesartan, the active metabolite of candesartan cilexetil, in vascular smooth muscle contraction studies, as well as in in vivo experiments on rat and in clinical studies, is compatible with its slow dissociation from, and continuous recycling between AT1-receptors. This recycling, or `rebinding' takes place because of the very high affinity of candesartan for the AT1-receptor.

Synthesis of N-Alkyl-1,2,4-oxadiazinones as Angiotensin-II (AT1) Receptor Antagonists

Heterocycles ◽  
1993 ◽  
Vol 36 (5) ◽  
pp. 1027 ◽  
Author(s):  
Harold N. Weller ◽  
Arthur V. Miller ◽  
Kenneth E. J. Dickinson ◽  
S. Anders Hedberg ◽  
Carol L. Delaney ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Receptor Antagonists ◽  
At1 Receptor Antagonists

Angiotensin II AT1 receptor antagonists and platelet activation

2001 ◽  
Vol 16 (suppl_1) ◽  
pp. 45-49 ◽  
Author(s):  
Antonio López‐Farré ◽  
Lourdes Sánchez de Miguel ◽  
Mercedes Montón ◽  
Ana Jiménez ◽  
Almudena Lopez‐Bloya ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Platelet Activation ◽  
At1 Receptor ◽  
Receptor Antagonists ◽  
At1 Receptor Antagonists

Comparative QSAR and pharmacophore analysis for a series of 2,4-dihydro-3H-1,2,4-triazol-3-ones derivatives as angiotensin II AT1 receptor antagonists

2013 ◽  
Vol 23 (5) ◽  
pp. 2486-2502 ◽  
Author(s):  
Mukesh C. Sharma ◽  
Smita Sharma ◽  
Pratibha Sharma ◽  
Ashok Kumar ◽  
Kamlendra Singh Bhadoriya
Keyword(s):  
Angiotensin Ii ◽  
At1 Receptor ◽  
Receptor Antagonists ◽  
At1 Receptor Antagonists

Angiotensin ii and its role in regulation of heart tolerance to ischemia/reperfusion inhibitors and angiotensin ii at1-receptor antagonists

2019 ◽  
pp. 118-126
Author(s):  
Л.Н. Маслов ◽  
Н.В. Нарыжная ◽  
С.Ю. Цибульников ◽  
Н.С. Воронков ◽  
Ю.В. Бушов
Keyword(s):  
Angiotensin Ii ◽  
Infarct Size ◽  
Ace Inhibitors ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Convincing Evidence ◽  
No Production ◽  
Receptor Antagonists ◽  
At1 Receptor Antagonists

Цель обзора - анализ данных о роли ангиотензина II в регуляции толерантности сердца к действию ишемии/реперфузии, а также анализ данных о кардиопротекторных свойствах ингибиторов ангиотензинпревращающего фермента (АПФ) и антагонистов АТ1-рецептора ангиотензина II. Установлено, что ангиотензин II оказывает инфаркт-лимитирующий эффект, который, по одним данным, связан с активацией АТ1-рецептора, по другим - является следствием стимуляции АТ2-рецептора. Кроме того, ангиотензин способствовал улучшению сократимости сердца в реперфузионном периоде, эффект был связан с активацией AT1-рецептора. Установлено, что ангиотензин II и АТ1-рецептор участвуют в инфаркт-лимитирующем эффекте ишемического прекондиционирования. Экспериментальные данные о способности антагонистов AT1-рецептора влиять на размер инфаркта носят противоречивый характер: есть сообщения о способности этих антагонистов оказывать инфаркт-лимитирующий эффект, есть данные об отсутствии у них подобного эффекта. Экспериментальные данные свидетельствуют, что ингибиторы АПФ оказывают инфаркт-лимитирующий эффект, который связан с увеличением уровня брадикинина и усилением продукции NO. Нет убедительных данных о том, ингибиторы АПФ и антагонисты АТ1-рецептора оказывают инфаркт-лимитирующий эффект у пациентов с острым инфарктом миокарда. Однако ингибиторы АПФ и антагонисты АТ1-рецептора препятствуют постинфарктному ремоделированию сердца. The review analyzes reports on the role of angiotensin II in regulation of heart tolerance to ischemia/reperfusion and cardioprotective properties of angiotensin converting enzyme (ACE) inhibitors and angiotensin II AT1-receptor antagonists. Angiotensin II is known to have an infarct-limiting effect, which according to some reports is associated with activation of the AT1 receptor and according to other reports results from stimulation of the AT2 receptor. In addition, angiotensin improves heart contractility during reperfusion, which is associated with activation of the AT1 receptor. Angiotensin II and AT1 receptor are also involved in the infarct-reducing effect of ischemic preconditioning. Experimental data on the ability of AT1 receptor antagonists to influence the infarct size are inconsistent; one study showed that these antagonists can exert an infarct-limiting effect whereas there is some evidence against such effect. Experimental studies have suggested that ACE inhibitors can restrict the infarct size, which is associated with increased bradykinin level and NO production. There is no convincing evidence that ACE inhibitors and AT1 receptor antagonists can restrict the infarct size in patients with acute myocardial infarction. However, ACE inhibitors and AT1 receptor antagonists prevent post-infarction heart remodeling.

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