Blood pressure and renal hemodynamic effects of angiotensin fragments

Yang, Rui; Smolders, Ilse Julia; Dupont, Alain

doi:10.1038/hr.2011.24

Cited by 37 publications

(27 citation statements)

References 146 publications

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“…The angiotensin II role in blood pressure regulation acts through central and peripheral mechanisms [ 107 ]. Since the ACE2 receptor is the medium through which SARS-CoV-2 infects mammalian cells, early concerns were raised about treating patients with pre-existing hypertension on ACE inhibitors or angiotensin II receptor blockers infected with the virus.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Brandão

Ramos

Dompieri

et al. 2021

Cytokine & Growth Factor Reviews

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Highlights Some inflammatory diseases are related to severe forms of COVID-19, characterized by an immune system overactivation. SARS-CoV-2 Spike protein binds with human innate immune receptors, mainly TLR4, increasing secretion of IL‐ 6 and TNF‐ α. The main inflammatory diseases seen as risk factors for COVID-19 are hypertension, diabetes, obesity, and atherosclerosis. The TLR4 signaling pathway is connected to inflammatory diseases seen as risk factors for COVID-19.

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Section: Toll-like Receptorsmentioning

confidence: 99%

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Brandão

Ramos

Dompieri

et al. 2021

Cytokine & Growth Factor Reviews

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“…ANG II signaling promotes vasoconstriction and elevation of blood pressure (32). By decreasing the concentration of ANG II and increasing the concentration of the heptapeptide ANG-(1-7), whose signaling tends to be opposite of that of ANG II, ACE2 can diminish the effects of ANG II, while loss of ACE2 exacerbates ANG II-driven processes (11,14).…”

mentioning

confidence: 99%

Species-specific inhibitor sensitivity of angiotensin-converting enzyme 2 (ACE2) and its implication for ACE2 activity assays

Pedersen

Sriramula

Chhabra

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Pedersen KB, Sriramula S, Chhabra KH, Xia H, Lazartigues E. Species-specific inhibitor sensitivity of angiotensin-converting enzyme 2 (ACE2) and its implication for ACE2 activity assays. Am J Physiol Regul Integr Comp Physiol 301: R1293-R1299, 2011. First published August 31, 2011 doi:10.1152/ajpregu.00339.2011.-Angiotensin-converting enzyme 2 (ACE2) is a component of the reninangiotensin system, and its expression and activity have been shown to be reduced in cardiovascular diseases. Enzymatic activity of ACE2 is commonly measured by hydrolysis of quenched fluorescent substrates in the absence or presence of an ACE2-specific inhibitor, such as the commercially available inhibitor DX600. Whereas recombinant human ACE2 is readily detected in mouse tissues using 1 M DX600 at pH 7.5, the endogenous ACE2 activity in mouse tissues is barely detectable. We compared human, mouse, and rat ACE2 overexpressed in cell lines for their sensitivity to inhibition by DX600. ACE2 from all three species could be inhibited by DX600, but the half maximal inhibitory concentration (IC50) for human ACE2 was much lower (78-fold) than for rodent ACE2. Following optimization of pH, substrate concentration, and antagonist concentration, rat and mouse ACE2 expressed in a cell line could be accurately quantified with 10 M DX600 (Ͼ95% inhibition) but not with 1 M DX600 (Ͻ75% inhibition). Validation that the optimized method robustly quantifies ACE2 in mouse tissues (kidney, brain, heart, and plasma) was performed using wild-type and ACE2 knockout mice. This study provides a reliable method for measuring human, as well as endogenous ACE2 activity in rodents. Our data underscore the importance of validating the effect of DX600 on ACE2 from each particular species at the experimental conditions employed. DX600; quenched fluorescent substrate; (7-methoxycoumarin-4-yl) acetyl-Ala-Pro-Lys(2,4-dinitrophenyl)-OH; enzyme inhibition ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) is a metallocarboxypeptidase that hydrolyzes the octapeptide ANG II, as well as several other small peptides (6,26,28). ANG II signaling promotes vasoconstriction and elevation of blood pressure (32). By decreasing the concentration of ANG II and increasing the concentration of the heptapeptide ANG-(1-7), whose signaling tends to be opposite of that of ANG II, ACE2 can diminish the effects of ANG II, while loss of ACE2 exacerbates ANG II-driven processes (11,14). To assess how ACE2 abundance affects biological processes, it is essential to be able to accurately quantify the enzymatic activity of ACE2, especially since there can be discordance in the regulation of ACE2 at the levels of mRNA, protein, and enzymatic activity (24,29,30). ACE2 activity is commonly quantified using the quenched fluorescent substrates (7-methoxycoumarin-4-yl)acetylTyr-Val-Ala-Asp-Ala-Pro-Lys(2,4-dinitrophenyl)-OH [Mca-YVADAPK(Dnp)] and (7-methoxycoumarin-4-yl)acetyl-AlaPro-Lys(2,4-dinitrophenyl)-OH [Mca-APK(Dnp)] (28). However, these fluorogenic substrates are not specific for ACE2. Mca-YVADAPK(Dnp) can, f...

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“…Findings obtained from studies of these novel RAS components have given us knowledge of novel roles of RAS in many research fields. 8 In 2006, Nagata et al 9 isolated a new AGT derivative, proangiotensin-12, from rat small intestine. This peptide is abundant in the small intestine, spleen, liver and the kidney.…”

mentioning

confidence: 99%

Regulation of a novel angiotensin II precursor, proangiotensin-12, in the tissues by blockade of the renin–angiotensin system

Satou

Kobori

2011

Hypertens Res

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Blood pressure and renal hemodynamic effects of angiotensin fragments

Cited by 37 publications

References 146 publications

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Species-specific inhibitor sensitivity of angiotensin-converting enzyme 2 (ACE2) and its implication for ACE2 activity assays

Regulation of a novel angiotensin II precursor, proangiotensin-12, in the tissues by blockade of the renin–angiotensin system

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