Angiotensin 1–7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo

Shefer, Gabi; Marcus, Yonit; Knoll, Esther; Dolkart, Oleg; Foichtwanger, Shulamit; Nevo, Nava; Limor, Rona; Stern, Naftali

doi:10.1161/hypertensionaha.116.07088

Cited by 19 publications

(16 citation statements)

References 29 publications

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“…In fact a number of noncanonical mechanisms of angiotensin pathways represent possible novel upstream targets to inhibit aldosterone/mineralocorticoid receptor-dependent pathways, for example, the ACE2/Ang-(1-7) pathway and their novel regulatory elements such as sheddases (ADAM 17) or apelin (which increases ACE2 promotor activity) [129], as well as Ang-(1-12)/chymase/Ang II pathway. As expected, interventions blocking Ang-(1-12)/chymase/Ang II as well as enhancing ACE2/Ang-(1-7) diminished aldosterone production [124,130]. It remains to be determined, however, which of the novel pharmacotherapies, shown to be effective in experimental heart failure including chymase inhibitors [131], recombinant human ACE2 [132][133][134], Ang-(1-7) [135], or combined angiotensin receptor antagonist and neprilysin inhibitor (ARNI) [104], are most effective in reducing the activity of aldosterone/mineralocorticoid receptor-dependent signaling.…”

Section: Resultssupporting

confidence: 72%

Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone

Tyrankiewicz¹,

Kij²,

Mohaissen³

et al. 2019

Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine

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Aldosterone plays an important role in the regulation of blood pressure, body fluid, and electrolyte homeostasis. Overactivation of aldosterone/ mineralocorticoid receptor (MR) pathway leads to hypertension, atherosclerosis, vascular damage, heart failure, and chronic kidney disease and is involved in many other diseases associated with endothelial dysfunction, inflammation, fibrosis, and metabolic disorders. Aldosterone is a final product of the renin-angiotensin-aldosterone system (RAAS), and its production is activated by angiotensin II, while angiotensin-(1-7) negatively regulates angiotensin II-mediated aldosterone production and in some experimental models inhibits aldosterone-induced damage in target tissues. In fact, the aldosterone/mineralocorticoid receptor-dependent pathway is regulated upstream by at least two major axes of RAAS: classical axis (ACE/Ang II) and nonclassical axis (ACE2/Ang-(1-7)). The relative balance between these two axes determines aldosterone production and activity. To better understand the regulation of aldosterone activity in physiology and diseases, it is important to analyze the role of aldosterone/mineralocorticoid receptor-dependent pathways in the context of upstream angiotensin pathways as some of the recently described mechanisms of RAAS represent possible novel upstream targets to inhibit aldosterone/mineralocorticoid receptor-dependent responses. In this review, we highlight the complexity of angiotensin pathways focusing on their role in various tissues in heart failure, with particular emphasis on nonclassical pathways including protective ACE2/Ang-(1-7) axis and detrimental Ang-(1-12)/chymase/Ang II axis.

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Section: Resultssupporting

confidence: 72%

Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone

Tyrankiewicz¹,

Kij²,

Mohaissen³

et al. 2019

Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine

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“…Indeed, Kawrazaki et al 35 demonstrated that aldosterone receptor activation and HSD intake induce inflammation and oxidative stress. In young (3-week-old) and adult (10-week-old) uninephrectomized Sprague-Dawley rats fed with a HSD, the aldosterone-induced organ damage was attenuated with eplerenone (aldosterone receptor antagonist), olmesartan (AT 1 R antagonist), and FAD286 (aldosterone synthase inhibitor) treatment.…”

Section: Discussionmentioning

confidence: 99%

“…It was suggested that severe hypertension and organ injury in young rats after HSD intake was primarily due to aldosterone receptor activation and secondarily to AT 1 R activation. 35 Figure 1 summarizes the course of activation of the two main arms of RAAS: ACE/Ang II/AT 1 R and ACE2/Ang-(1-7)/MAS in tissue. We highlighted in this figure the ACE/ACE2 ratio determining the fate of the system during HSD intake and the AT 1 R responses as the end point of the inappropriate RAAS activation.…”

Section: Discussionmentioning

confidence: 99%

Inappropriate activity of local renin-angiotensin-aldosterone system during high salt intake: impact on the cardio-renal axis

et al. 2018

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Atividade inadequada do sistema renina-angiotensina-aldosterona local durante período de alta ingestão de sal: impacto sobre o eixo cardiorrenal Apesar de haver uma concordância geral sobre a necessidade de redução na ingestão de sal como questão de saúde publica, o mecanismo pelo qual a alta ingesta de sal deflagra efeitos patológicos sobre o eixo cardiorrenal não está ainda completamente elucidado. Cada vez mais evidencias indicam que o sistema renina-angiotensinaaldosterona (S-RAA) seja o principal alvo da alta ingesta de Na + . Uma ativação inadequada do S-RAA tecidual pode causar hipertensão e dano ao órgão. Nós revisamos o impacto da dieta com alto teor de sódio sobre o eixo cardiorrenal, destacando as vias moleculares que causam a lesão. Também fizemos uma avaliação de recentes estudos observacionais relacionados às consequên-cias do acúmulo de Na + não osmoticamente ativo, quebrando assim o paradigma de que a alta ingestão de sódio necessariamente aumenta a concentração sérica de Na + , assim promovendo a retenção de água. ResumoPalavras-chave: Renina; Angiotensina II; Sódio na Dieta; Rim; Coração.Although there is a general agreement on the recommendation for reduced salt intake as a public health issue, the mechanism by which high salt intake triggers pathological effects on the cardio--renal axis is not completely understood. Emerging evidence indicates that the renin-angiotensin-aldosterone system (RAAS) is the main target of high Na + intake. An inappropriate activation of tissue RAAS may lead to hypertension and organ damage. We reviewed the impact of high salt intake on the RAAS on the cardio-renal axis highlighting the molecular pathways that leads to injury effects. We also provide an assessment of recent observational studies related to the consequences of non-osmotically active Na + accumulation, breaking the paradigm that high salt intake necessarily increases plasma Na + concentration promoting water retention AbstRAct

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“…Reports suggest that the levels of angiotensinogen, Ang II, and mineralocorticoids are increased in pregnancy and lead to preeclampsia [ 11 , 24 ]. Further, to regulate this increased blood pressure, a compensatory increase in ACE 2 activity leads to the production of Ang (1–7) which causes vasodilation, reduces the production of aldosterone by acting on adrenal glomerulosa cells [ 23 , [25] , [26] , [27] , [28] ]. ACE 2 has an antihypertrophic activity that plays a pivotal role in cardiac tissue during the gestational period and may modulate myocardial tissue growth [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Is highly expressed ACE 2 in pregnant women “a curse” in times of COVID-19 pandemic?

et al. 2021

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Angiotensin-converting enzyme 2 (ACE 2) is a membrane-bound enzyme that cleaves angiotensin II (Ang II) into angiotensin (1–7). It also serves as an important binding site for SARS-CoV-2, thereby, facilitating viral entry into target host cells. ACE 2 is abundantly present in the intestine, kidney, heart, lungs, and fetal tissues. Fetal ACE 2 is involved in myocardium growth, lungs and brain development. ACE 2 is highly expressed in pregnant women to compensate preeclampsia by modulating angiotensin (1–7) which binds to the Mas receptor, having vasodilator action and maintain fluid homeostasis. There are reports available on Zika, H1N1 and SARS-CoV where these viruses have shown to produce fetal defects but very little is known about SARS-CoV-2 involvement in pregnancy, but it might have the potential to interact with fetal ACE 2 and enhance COVID-19 transmission to the fetus, leading to fetal morbidity and mortality. This review sheds light on a path of SARS-CoV-2 transmission risk in pregnancy and its possible link with fetal ACE 2.

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Angiotensin 1–7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo

Cited by 19 publications

References 29 publications

Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone

Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone

Inappropriate activity of local renin-angiotensin-aldosterone system during high salt intake: impact on the cardio-renal axis

Is highly expressed ACE 2 in pregnant women “a curse” in times of COVID-19 pandemic?

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