New Components of the Renin-Angiotensin System: Alamandine and the Mas-Related G Protein-Coupled Receptor D

Etelvino, Gisele; Peluso, Augusto; Santos, Robson A.S.

doi:10.1007/s11906-014-0433-0

Cited by 73 publications

(49 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5 It binds to MrgD receptors. 5,9, 10 The only difference between alamandine and Ang-(1-7) is the existence of an N-terminal alanine residue (Ala1) in alamandine. 5 Alamandine can be formed in the rat heart after perfusion with Ang-(1-7).…”

mentioning

confidence: 99%

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

Javanmardi

Kouhpayeh

et al. 2017

Circ J

View full text Add to dashboard Cite

angiotensin II type 1 receptor (AT1R) blockers. These drugs block angiotensin II (Ang II) -the primary active peptide in the RAS, which has many effects on blood vessels, the heart, the brain and the kidneys -from activating AT1R. AT1R is one of the two well-characterized receptors that Ang II activates (in addition to angiotensin II type 2 receptor (AT2R)). 3 Losartan is an angiotensin receptor blocker, 4 which mainly antagonizes AT1R, while PD123319 can block AT2R and Mas-related G protein-coupled receptor D (MrgD) receptors. 5 Recently, numerous researchers have shown that the RAS has additional complex multifunctional peptides, enzymes and receptors. The discovery of the ACE2/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, 6,7 which counterbalances several functions of the ACE/Ang II/AT1R axis, has highlighted the complexity of the RAS. The ACE2/Ang-(1-7)/ Mas receptor axis acts as a counter-regulatory axis. 7 It involves the heptapeptide peptide known as Ang-(1-7), which acts through a G-protein-coupled receptor called Mas. 7 Ang-(1-7) can be hydrolyzed from Ang II by the action of peptidases such as ACE2 and prolyl endopepti-D espite major progress in the research on the pathogenesis and management of hypertension and other aspects of cardiometabolic disease, these conditions underlie a significant number cases of morbidity and mortality due to cardiovascular and chronic kidney disease. It is predicted that there will be an increase in the hypertension prevalence rate in the United States (US). Currently, this condition affects 29% of the population in this country; that is, ~65 million individuals. 1 The significance of the renin-angiotensin system (RAS) in the development of hypertension and cardiovascular disease is well known. 2 Chronic RAS activation is a significant causal factor associated with the gradual malfunction of organs such as blood vessels, the kidneys and the heart. 2 These consequences of RAS activation have encouraged the development of medicines that can deactivate the RAS and thereby prevent the associated pathologies. The first class of drugs aimed at RAS inhibition are known as angiotensin-converting enzyme (ACE1) inhibitors, and they came on the market in the late 1970 s. Background: Alamandine is a newly discovered component of the renin-angiotensin system, which regulates blood pressure. In this study, the effect of alamandine on cardiovascular parameters in two-kidney, one clip (2K1C) hypertensive rats and normotensive rats, and the possible roles of the angiotensin II type 1 receptor (AT1R) and the PD123319-sensitive receptors in mediating this effect was investigated.

show abstract

mentioning

confidence: 99%

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

Javanmardi

Kouhpayeh

et al. 2017

Circ J

View full text Add to dashboard Cite

show abstract

“…Alamandine acts through binding to the receptor MrgD (Lautner et al 2013; Hrenak et al 2016; Etelvino et al 2014). In the present study, we found that MrgD expression was higher in the hearts of SHRs than those of WKY rats, and Ang II treatment increased MrgD levels in cardiomyocytes, which suggest that alamandine receptor activity is enhanced in the heart during hypertension and cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats

et al. 2018

View full text Add to dashboard Cite

Oral administration of the peptide alamandine has antihypertensive and anti-fibrotic effects in rats. This work aimed to determine whether subcutaneous alamandine injection would attenuate hypertension and cardiac hypertrophy, and improve the function of a major target of hypertension-related damage, the left ventricle (LV), in spontaneously hypertensive rats (SHRs). This was examined in vivo in SHRs and normotensive rats subjected to 6-week subcutaneous infusion of alamandine or saline control, and in vitro in H9C2-derived and primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Tail artery blood pressure measurement and transthoracic echocardiography showed that hypertension and impaired LV function in SHRs were ameliorated upon alamandine infusion. Alamandine administration also decreased the mass gains of heart and lung in SHRs, suppressed cardiomyocyte cross-sectional area expansion, and inhibited the mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. The expression of alamandine receptor Mas-related G protein-coupled receptor, member D was increased in SHR hearts and in cardiomyocytes treated with Ang II. Alamandine inhibited the increases of protein kinase A (PKA) levels in the heart in SHRs and in cardiomyocytes treated with Ang II. In conclusion, the present study showed that alamandine administration attenuates hypertension, alleviates cardiac hypertrophy, and improves LV function. PKA signaling may be involved in the mechanisms underlying these effects.

show abstract

“…Namely, Santos et al demonstrated that Ang-(1-7) is the ligand for the G-protein-coupled receptor Mas, and that the ACE2-Ang-(1-7)-Mas axis is the counter-regulating of the actions of classical RAS [4,5]. Also, a variety of biologically active peptides, novel components of the RAS have been found recently: proangiotensin-12 (angiotensin-(1-12)) [6], angiotensin A (Ang A) [7,8] and alamandine [9,10].…”

Section: Short Overview Of the Rasmentioning

confidence: 99%

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Kolaković¹,

Živković²,

Stanković³

2017

Renin-Angiotensin System - Past, Present and Future

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

show abstract

New Components of the Renin-Angiotensin System: Alamandine and the Mas-Related G Protein-Coupled Receptor D

Cited by 73 publications

References 49 publications

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Contact Info

Product

Resources

About