Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II

Shaltout, Hossam A.; Westwood, Brian; Averill, David B.; Ferrario, Carlos M.; Figueroa, Jorge; Diz, Debra I.; Rose, James C.; Chappell, Mark C.

doi:10.1152/ajprenal.00139.2006

Cited by 129 publications

(158 citation statements)

References 38 publications

(45 reference statements)

Supporting

Mentioning

151

Contrasting

Order By: Relevance

“…Recent studies confirmed that NEP can metabolize Ang I directly into Ang-(1-7), and, furthermore, NEP can act upon Ang II to yield Ang-(1-4) and Ang-(3-4), but not Ang-(1-7) in sheep renal proximal tubular membranes (Shaltout et al 2007). …”

Section: Neprilysin 2411mentioning

confidence: 93%

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

Trask

Ferrario

2007

Cardiovascular Drug Reviews

Self Cite

100

View full text Add to dashboard Cite

Many advances have been made in the cardiovascular field in the last several decades. Among them is the progress completed to date on the heptapeptide member of the reninangiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)]. The peptide's beneficial actions against pathophysiological processes, such as cardiac arrhythmia, heart failure, hypertension, renal disease, preeclampsia, and even cancer are continuously being uncovered. This review encompasses the pharmacology of Ang-(1-7) and expounds upon the peptide's potential as a therapeutic agent against pathological processes both within and outside the cardiovascular continuum.

show abstract

Section: Neprilysin 2411mentioning

confidence: 93%

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

Trask

Ferrario

2007

Cardiovascular Drug Reviews

Self Cite

100

View full text Add to dashboard Cite

show abstract

“…28,29 Besides, kinetic differences in AngI and AngII metabolism are shown to be exist between rat, human and sheep kidneys. 25,30,31 There are some limitations to our study. First, our data were obtained in adult animals with established hypertension and hence do not rule out a role for renal ACE2 in the early onset of hypertension.…”

Section: Controlsmentioning

confidence: 97%

Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

et al. 2009

View full text Add to dashboard Cite

Differential renal expression of a homolog of the angiotensin-converting enzyme (ACE), that is, ACE2, has been implicated as a genetic basis of polygenetic hypertension in the stroke-prone spontaneously hypertensive rat model. However, data on the role of ACE2 in hypertension are still inconclusive. Therefore, we analyzed kidney ACE2 mRNA, ACE2 protein and ACE2 enzyme activities in the adult polygenetic stroke-prone spontaneously hypertensive rat (SHRSP) and the monogenetic TGR(mREN2)27 rat models, in comparison with their normotensive reference strains, Wistar-Kyoto (WKY) and Spraque-Dawley (SD) rats, respectively. Kidney ACE2 mRNA was studied using quantitative real-time reverse transcriptase-PCR (RT-PCR) in cortex and medulla, whereas protein expression was scored semiquantitatively in detail in different renal structures using immunohistochemistry. Furthermore, total renal tissue ACE2 activity was measured using a fluorimetric assay that was specified by the ACE2 inhibitor DX600. In SHRSP and homozygous TGR(mREN2)27 rats with established hypertension, kidney ACE2 mRNA, protein and tissue ACE2 activities were not different from their respective WKY and SD reference strain, respectively. In addition, when we looked at renal localization, we found ACE2 protein to be predominantly present in glomeruli and endothelium with weak staining in distal and negative staining in proximal tubuli. Thus, our data challenge previous work that implicates ACE2 as a candidate gene for hypertension in SHRSP by reporting a significant reduction of ACE2 in the kidneys of SHRSP. Taken together, renal ACE2 is not altered in the SHRSP and TGR(mREN2)27 genetic rat models with established hypertension.

show abstract

“…It is widely accepted that small peptides derived from Ang Ⅱ have local physiological effects, especially in the kidney (Figure 1). ACE2 is a transmembrane glycoprotein that shares a 42% of homology with ACE and contains a single active site domain more closely to the N domain of ACE [16,38] . Unlike ACE, ACE2 is a monocarboxypeptidase, generating Ang-(1-7) by the cleavage of a single Phe residue from Ang Ⅱ, and Ang-(1-9), removing the C-terminal Leu residue from Ang Ⅰ [16,38] .…”

Section: New Members Of Ras: Ang Ii-derived Peptidesmentioning

confidence: 99%

“…ACE2 is a transmembrane glycoprotein that shares a 42% of homology with ACE and contains a single active site domain more closely to the N domain of ACE [16,38] . Unlike ACE, ACE2 is a monocarboxypeptidase, generating Ang-(1-7) by the cleavage of a single Phe residue from Ang Ⅱ, and Ang-(1-9), removing the C-terminal Leu residue from Ang Ⅰ [16,38] . Within the renal brush-border vesicles of the rat, Ang-(1-7) is preferentially hydrolyzed by aminopeptidases and neprylisin (NEP) after aminopeptidase blockade, generating Ang-(1-4) [39] .…”

Section: New Members Of Ras: Ang Ii-derived Peptidesmentioning

confidence: 99%

“…New RAS members and hypertension treatment renal NEP Ang I is hydrolyzed primarily to Ang-(1-7) and Ang-(1-4) [40,41] . In sheep proximal tubules, urine and serum, Ang Ⅱ is converted to Ang-(1-7) by both membrane-bound and soluble forms of ACE2 [38] . The physiological importance of Ang-(1-7) has become increasingly evident, especially after Santos et al [14] found a G protein-coupled receptor for Ang-(1-7), the Mas receptor, using a selective Ang-(1-7) antagonist.…”

Section: New Members Of Ras: Ang Ii-derived Peptidesmentioning

confidence: 99%

See 1 more Smart Citation

Renin-angiotensin system in the kidney: What is new?

Ferrão

Lara

Lowe

2014

WJN

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin Ⅱ (Ang Ⅱ) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang Ⅱ formation or even active Ang Ⅱ-derived peptides have now been described acting on Ang Ⅱ AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang Ⅱ formation. This in situ formation, especially in the kidney, increases Ang Ⅱ levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang Ⅱ effects, improves the development of new drugs for treating hypertension and cardiovascular diseases. Key words: Renin-angiotensin system; Angiotensin Ⅱ; Kidney; Hypertension treatment; Receptor Core tip: Activation of the angiotensin converting enzyme (ACE)/ Angiotensin Ⅱ (Ang Ⅱ)/AT1 axis leads to vasoconstriction, anti-diuresis, anti-natriuresis, release of aldosterone and anti-diuretic hormone, which can result in hypertension, renal and cardiovascular diseases. Inhibition of renin and ACE or blocking AT1 receptor is the most used therapies for heart failure and hypertension. Nevertheless, the discovery of local Ang Ⅱ synthesis, new Ang Ⅱ metabolites, receptors and axis of this system, makes possible the development of new drugs and strategies for renal and cardiovascular diseases treatment, such as activation of ACE2/Ang-(1-7)/ Mas axis, which presents opposite effects of AT1 activation by Ang Ⅱ.

show abstract

Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin II

Cited by 129 publications

References 38 publications

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

Angiotensin‐(1‐7): Pharmacology and New Perspectives in Cardiovascular Treatments

Renal ACE2 expression and activity is unaltered during established hypertension in adult SHRSP and TGR(mREN2)27

Renin-angiotensin system in the kidney: What is new?

Contact Info

Product

Resources

About