Regulation of angiotensin-(1–7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

Zong, Wen-na; Yang, Xiaohui; Xiumei, Chen; Huang, Hongjuan; Zheng, Hongjian; Qin, Xiaoyi; Yong, Yonghong; Cao, Kejiang; Huang, Jun; Lu, Xiyi

doi:10.1038/aps.2011.96

Cited by 37 publications

(29 citation statements)

References 29 publications

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“…Moreover, Losartan also increased renal expression of ACE2, the main responsible for Ang-(1–7) synthesis at renal tissue [53]. Corroborating the present data, previous studies reported similar effects of ARBs on the modulation of ACE2Ang-(1–7)/Mas receptor axis at different sites [54]–[58]. In this regard, Ferrario et al (2005) showed that Losartan increases plasma and urinary levels of Ang-(1–7) and renal ACE2 activity, without changing the expression of Mas receptor, AT 1 or ACE in Lewis rats.…”

Section: Discussionsupporting

confidence: 90%

“…Igase et al (2011) in a model of hypertensive nephropathy showed that olmesartan treatment increased plasma levels of Ang-(1–7) leading to cardiprotective and renoprotective effects [55]. In a model of ADR-induced heart failure in Male Sprague-Dawley rats, Zong et al (2011) detected a decrease of plasma Ang-(1–7) levels and reduced myocardial expression of Mas receptor, while the treatment with telmisartan or losartan increased Ang-(1–7) levels and suppressed myocardial AT 1 receptor expression without changing the expression of Mas [58]. Recent studies of Sukumaran et al (2011 and 2012) showed that the protein and mRNA levels of Mas receptor, ACE2 and Ang-(1–7) were upregulated in olmesartan treated group in experimental autoimmune myocarditis and these changes in RAS components decreased the expression of inflammatory markers [56], [57].…”

Section: Discussionmentioning

confidence: 99%

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Beneficial Effects of the Activation of the Angiotensin-(1–7) Mas Receptor in a Murine Model of Adriamycin-Induced Nephropathy

et al. 2013

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Angiotensin-(1–7) [Ang-(1–7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-β. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas+/+) and Mas knockout (Mas −/−) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas+/+, but not in Mas −/− mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1–7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of the Activation of the Angiotensin-(1–7) Mas Receptor in a Murine Model of Adriamycin-Induced Nephropathy

et al. 2013

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“…This notion is further emphasized by the recent discovery of MrgD as another novel receptor for Ang- (1-7) regulating the physiological arterial pressure. 9 Physiological relevance of the Ang-(1-7)/AT1-R axis could be, however, questioned given that the affinity/potency of Ang-(1-7) for AT1-R is modest (≈300 nmol/L) and relatively far from plasma concentrations generally described, with significant differences in between rodents (nmol/L) 26,27 or human species (pM). [28][29][30] Nevertheless, despite the RAAS was originally described as a circulating system, it is now widely accepted that a distinct local RAAS does exist in several tissues, 31 thus promoting a close ligand-receptor proximity to ensure an accurate spatiotemporal regulation of RAAS actions similar to that observed for neurotransmitters concentrations in the synaptic cleft after release.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

et al. 2016

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Hyperactivity of the renin–angiotensin–aldosterone system through the angiotensin II (Ang II)/Ang II type 1 receptor (AT1-R) axis constitutes a hallmark of hypertension. Recent findings indicate that only a subset of AT1-R signaling pathways is cardiodeleterious, and their selective inhibition by biased ligands promotes therapeutic benefit. To date, only synthetic biased ligands have been described, and whether natural renin–angiotensin–aldosterone system peptides exhibit functional selectivity at AT1-R remains unknown. In this study, we systematically determined efficacy and potency of Ang II, Ang III, Ang IV, and Ang-(1–7) in AT1-R–expressing HEK293T cells on the activation of cardiodeleterious G-proteins and cardioprotective β-arrestin2. Ang III and Ang IV fully activate similar G-proteins than Ang II, the prototypical AT1-R agonist, despite weaker potency of Ang IV. Interestingly, Ang-(1–7) that binds AT1-R fails to promote G-protein activation but behaves as a competitive antagonist for Ang II/Gi and Ang II/Gq pathways. Conversely, all renin–angiotensin–aldosterone system peptides act as agonists on the AT1-R/β-arrestin2 axis but display biased activities relative to Ang II as indicated by their differences in potency and AT1-R/β-arrestin2 intracellular routing. Importantly, we reveal Ang-(1–7) a known Mas receptor-specific ligand, as an AT1-R–biased agonist, selectively promoting β-arrestin activation while blocking the detrimental Ang II/AT1-R/Gq axis. This original pharmacological profile of Ang-(1–7) at AT1-R, similar to that of synthetic AT1-R–biased agonists, could, in part, contribute to its cardiovascular benefits. Accordingly, in vivo, Ang-(1–7) counteracts the phenylephrine-induced aorta contraction, which was blunted in AT1-R knockout mice. Collectively, these data suggest that Ang-(1–7) natural-biased agonism at AT1-R could fine-tune the physiology of the renin–angiotensin–aldosterone system.

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“…In addition, losartan treatment protected skeletal muscle against disuse atrophy . Interestingly, several studies have demonstrated that ACEi or ARB treatments not only inhibit ACE or AT‐1 blockade, respectively, but also increase Ang (1–7) levels, probably by an attenuation of its degradation (see Fig. ).…”

Section: Contribution Of Ras Axis To Muscle Pathologiesmentioning

confidence: 94%

Renin‐Angiotensin System: An Old Player with Novel Functions in Skeletal Muscle

Cabello-Verrugio

Morales

Rivera

et al. 2015

Medicinal Research Reviews

140

142

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Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle.

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Regulation of angiotensin-(1–7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

Cited by 37 publications

References 29 publications

Beneficial Effects of the Activation of the Angiotensin-(1–7) Mas Receptor in a Murine Model of Adriamycin-Induced Nephropathy

Beneficial Effects of the Activation of the Angiotensin-(1–7) Mas Receptor in a Murine Model of Adriamycin-Induced Nephropathy

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

Renin‐Angiotensin System: An Old Player with Novel Functions in Skeletal Muscle

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