Involvement of the Gi/o/cGMP/PKG pathway in the AT2-mediated inhibition of outer cortex proximal tubule Na+-ATPase by Ang-(1–7)

Lara, Lucienne S.; Cavalcante, Fabíola; Axelband, Flavia; Souza, A.M. De; Lopes, Anibal Gil; Caruso-Neves, Celso

doi:10.1042/bj20051455

Cited by 65 publications

(36 citation statements)

References 48 publications

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“…However, Ang (1-7) evoked vasorelaxation in pig coronary arteries that was attenuated by the AT 2 R antagonist, PD123319, suggesting an AT 2 R involvement [27]. Subsequent studies confirmed that Ang (1-7) can mediate its effects via AT 2 R [8–10]. Ang (1-7)-stimulated NO release in bovine aortic endothelial cells was markedly attenuated by AT 2 R inhibition ( ∼ 90%) [28, 29] and to a lesser extent by Mas R inhibition ( ∼ 50%) [28], suggesting activation of multiple receptors by Ang (1-7) which is also consistent with Ang (1-7)-stimulated arachidonic acid release in rabbit vascular smooth muscle cells [30].…”

Section: Discussionmentioning

confidence: 99%

Differential Mechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats

Bosnyak

Widdop

Denton

et al. 2012

International Journal of Hypertension

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Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT2R). However, the role of vascular AT2R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (~17 weeks) and aged (~19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT1R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT2R antagonist, PD123319. In a separate group of animals, the specific MasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT2R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT2R blockade or MasR blockade. At the same time, AT2R, MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT2R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT2R and MasR.

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Section: Discussionmentioning

confidence: 99%

Differential Mechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats

Bosnyak

Widdop

Denton

et al. 2012

International Journal of Hypertension

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“…In these animals, Ang-(1-7) produced a substantial decrease in blood pressure, which was not modified by the Ang-(1-7) receptor antagonist A-779 but was fully blocked by the AT 2 antagonist PD 123319. There are few other reports in which an effect of Ang-(1-7) was blocked or attenuated by PD 123319 but not by A-779 (De Souza et al 2004, Lara et al 2006, Pereyra-Alfonso et al 2007.…”

Section: Metabolic Actions Of the Ace2/ang-(1-7)/mas Axismentioning

confidence: 96%

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Santos

Ferreira

Verano‐Braga

et al. 2012

Journal of Endocrinology

421

357

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Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the reninangiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/ proliferative arm of the RAS consisting of ACE, Ang II, and AT 1 receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1-7) and Mas with AT 1 and AT 2 receptors.

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“…[11][12][13] Moreover, several studies have shown that the interaction of Ang-(1-7) with Mas evokes numerous protective cardiovascular actions, such as nitric oxide ( NO) 14,15 release, Akt phosphorylation 16 and vasodilation ( Figure 2). 17 Nevertheless, other studies indicate that Ang-(1-7) may function through angiotensin type 2 receptor 18 and that Mas can antagonize the actions of the angiotensin type 1 receptor. 19,20 The local activity of ACE2 determines the relative levels of the vasoconstrictor and pro-oxidative peptide Ang II and its vasodilatory and antioxidative metabolite Ang-(1-7) at the corresponding receptors ( Figure 2).…”

Section: The Classic Pathway and The Novel Components Of The Renin-anmentioning

confidence: 99%

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

2010

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The renin-angiotensin-aldosterone system (RAAS) is a pivotal regulator of physiological homeostasis and diseases of the cardiovascular system. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas. This newly defined ACE2-angiotensin-(1-7)-Mas axis was shown to have a critical role in the vasculature and in the heart, exerting mainly protective effects. One important mechanism of the classic and the new RAAS regulate vascular function is through the regulation of redox signaling. Angiotensin II is a classic prooxidant peptide that increases superoxide production through the activation of NAD(P)H oxidases. This review summarizes the current knowledge about the ACE2-angiotensin-(1-7)-Mas axis and redox signaling in the context of cardiovascular regulation and disease. By interacting with its receptor Mas, angiotensin-(1-7) induces the release of nitric oxide from endothelial cells and thereby counteracts the effects of angiotensin II. ACE2 converts angiotensin II to angiotensin-(1-7) and, thus, is a pivotal regulator of the local effects of the RAAS on the vessel wall. Taken together, the ACE2-angiotensin-(1-7)-Mas axis emerges as a novel therapeutic target in the context of cardiovascular and metabolic diseases.

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Involvement of the Gi/o/cGMP/PKG pathway in the AT2-mediated inhibition of outer cortex proximal tubule Na+-ATPase by Ang-(1–7)

Cited by 65 publications

References 48 publications

Differential Mechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats

Differential Mechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

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