Comparison of Angiotensin II Type-1 and Type-2 Receptor Antagonists on Angiotensin II– Induced IP3 Generation in Cardiomyocytes

Goutsouliak, Valeri; Rabkin, Simon W.

doi:10.1016/s0306-3623(97)00270-x

Cited by 15 publications

(8 citation statements)

References 38 publications

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“…Angiotensin I, the precursor of angiotensin II, showed effects similar to those of angiotensin II (Figure 2, Table 2). The existence of the angiotensin-converting enzyme in the vascular endothelial cells and the conversion of angiotensin I to angiotensin II was reported in the pulmonary blood vessels [60,61]. In the present study, results with captopril and chymostatin indicated that the angiotensin-converting enzyme, but not chymase, was involved in the conversion of angiotensin I to angiotensin II in the guinea pig pulmonary vein.…”

Section: Discussionsupporting

confidence: 62%

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Tanaka

Obata

Ohmori

et al. 2019

IJMS

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The automaticity of the pulmonary vein myocardium is known to be the major cause of atrial fibrillation. We examined the involvement of angiotensin II in the automatic activity of isolated guinea pig pulmonary vein preparations. In tissue preparations, application of angiotensin II induced an automatic contractile activity; this effect was mimicked by angiotensin I and blocked by losartan, but not by PD123,319 or carvedilol. In cardiomyocytes, application of angiotensin II induced an increase in the frequency of spontaneous Ca2+ sparks and the generation of Ca2+ transients; these effects were inhibited by losartan or xestospongin C. In tissue preparations, angiotensin II caused membrane potential oscillations, which lead to repetitive generation of action potentials. Angiotensin II increased the diastolic depolarization slope of the spontaneous or evoked action potentials. These effects of angiotensin II were inhibited by SEA0400. In tissue preparations showing spontaneous firing of action potentials, losartan, xestospongin C or SEA0400 decreased the slope of the diastolic depolarization and inhibited the firing of action potentials. In conclusion, in the guinea pig pulmonary vein myocardium, angiotensin II induces the generation of automatic activity through activation of the IP3 receptor and the Na+-Ca2+ exchanger.

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Section: Discussionsupporting

confidence: 62%

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Tanaka

Obata

Ohmori

et al. 2019

IJMS

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“…Ang-2 signals are received by two main isoforms of the Ang-2 receptor-Type 1 (AT-1) and Type 2 (AT-2). Cells from different animals contain different proportions of each although the proportion is approximately equal in rodents such as the rat (20). There is evidence linking AT-1 receptors to PLCb, IP3 production, and calcium release via G q family GPCRs (21)(22)(23).…”

Section: Methodsmentioning

confidence: 99%

Modeling Hypertrophic IP3 Transients in the Cardiac Myocyte

Cooling

Hunter

Crampin

2007

Biophysical Journal

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Cardiac hypertrophy is a known risk factor for heart disease, and at the cellular level is caused by a complex interaction of signal transduction pathways. The IP3-calcineurin pathway plays an important role in stimulating the transcription factor NFAT which binds to DNA cooperatively with other hypertrophic transcription factors. Using available kinetic data, we construct a mathematical model of the IP3 signal production system after stimulation by a hypertrophic alpha-adrenergic agonist (endothelin-1) in the mouse atrial cardiac myocyte. We use a global sensitivity analysis to identify key controlling parameters with respect to the resultant IP3 transient, including the phosphorylation of cell-membrane receptors, the ligand strength and binding kinetics to precoupled (with G(alpha)GDP) receptor, and the kinetics associated with precoupling the receptors. We show that the kinetics associated with the receptor system contribute to the behavior of the system to a great extent, with precoupled receptors driving the response to extracellular ligand. Finally, by reparameterizing for a second hypertrophic alpha-adrenergic agonist, angiotensin-II, we show that differences in key receptor kinetic and membrane density parameters are sufficient to explain different observed IP3 transients in essentially the same pathway.

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“…Combined treatment with losartan and PD‐123319 proved to be more effective in attenuating the reflex increase in plasma adrenaline concentrations during insulin‐induced hypoglycaemia than either of the two AngII receptor antagonists given alone 60 . The combination of both AT 1 and AT 2 receptor antagonists, at concentrations that each partly reduced inositol 1,4,5‐trisphosphate (IP 3 ), completely inhibited IP 3 formation, suggesting that both receptors are necessary for the actions of AngII mediated by the IP 3 signal transduction pathway 61 …”

Section: Cardiac Effects Mediated By At2 Receptorsmentioning

confidence: 99%

Role of angiotensin AT₁ and AT₂ receptors in cardiac hypertrophy and cardiac remodelling

Zhu

Lü

et al. 2003

Clin Exp Pharma Physio

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SUMMARY1. Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. Angiotensin AT 1 receptor antagonism has been considered as a specific approach to block the renin-angiotensin system and been demonstrated to be able to prevent or regress LVH by interfering with the remodelling process of the heart. 2. Angiotensin AT 1 receptor blockade induces a marked increase in angiotensin (Ang) II, which may stimulate the AT 2 receptors. Gene expression of AT 1 and AT 2 receptors increases in a time-dependent manner in cardiac remodelling following myocardial infarction.3. Considerable efforts have been made to clarify the role of AT 2 receptors in cardiac hypertrophy and remodelling since the mid-1990s, resulting in controversial reports: the AT 2 receptor mediates actions either opposite to or in coordination with those of the AT 1 receptor. Moreover, there are many reports of no significant effects mediated by AT 2 receptors. 4. Based on the studies reviewed in the present article, we assume that the predominant effect of AngII in cardiac hypertrophy and cardiac remodelling is growth promoting and that this effect is mediated mainly via AT 1 receptors. The AT 2 receptors may affect the hypertrophic process by interacting with other cardiac membrane proteins, enzymes and autacoids. Before coming to a conclusion as to whether AT 2 receptor stimulation or antagonism is beneficial to the heart, more studies should be performed in different LVH models, especially long-term treatment protocols in vivo .

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Comparison of Angiotensin II Type-1 and Type-2 Receptor Antagonists on Angiotensin II– Induced IP3 Generation in Cardiomyocytes

Cited by 15 publications

References 38 publications

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Modeling Hypertrophic IP3 Transients in the Cardiac Myocyte

Role of angiotensin AT₁ and AT₂ receptors in cardiac hypertrophy and cardiac remodelling

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Comparison of Angiotensin II Type-1 and Type-2 Receptor Antagonists on Angiotensin II– Induced IP3 Generation in Cardiomyocytes

Cited by 15 publications

References 38 publications

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Angiotensin II Induces Automatic Activity of the Isolated Guinea Pig Pulmonary Vein Myocardium through Activation of the IP3 Receptor and the Na+-Ca2+ Exchanger

Modeling Hypertrophic IP3 Transients in the Cardiac Myocyte

Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling

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Role of angiotensin AT₁ and AT₂ receptors in cardiac hypertrophy and cardiac remodelling