Counterregulatory Actions of Angiotensin-(1-7)

Ferrario, Carlos M.; Chappell, Mark C.; Tallant, E. Ann; Brosnihan, K. Bridget; Diz, Debra I.

doi:10.1161/01.hyp.30.3.535

Cited by 474 publications

(443 citation statements)

References 53 publications

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“…Ang II is a potent vasoconstrictor that promotes vascular hypertrophy (14). The in vitro ACE2-catalyzed hydrolysis of Ang II produces Ang 1-7, whose vasodilator and antihypertensive effects are counter to those of Ang II (15,16 in a tissue-specific manner. Studies to examine the in vivo effects of ACE2 inhibition on Ang II serum levels and on blood pressure will help us to understand the physiological role of the carboxypeptidase.…”

Section: Discussionmentioning

confidence: 99%

Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase

Vickers¹,

Hales²,

Kaushik³

et al. 2002

Journal of Biological Chemistry

1,302

1,394

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Human angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a zinc metalloprotease whose closest homolog is angiotensin I-converting enzyme. To begin to elucidate the physiological role of ACE2, ACE2 was purified, and its catalytic activity was characterized. ACE2 proteolytic activity has a pH optimum of 6.5 and is enhanced by monovalent anions, which is consistent with the activity of ACE. ACE2 activity is increased ϳ10-fold by Cl ؊ and F ؊ but is unaffected by Br ؊ . ACE2 was screened for hydrolytic activity against a panel of 126 biological peptides, using liquid chromatographymass spectrometry detection. Eleven of the peptides were hydrolyzed by ACE2, and in each case, the proteolytic activity resulted in removal of the C-terminal residue only.

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Section: Discussionmentioning

confidence: 99%

Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase

Vickers¹,

Hales²,

Kaushik³

et al. 2002

Journal of Biological Chemistry

1,302

1,394

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“…NEP is found in the lung, gut, adrenal glands, brain, and in the heart 2,3 and cleaves several endogenous vasodilator and vasoconstrictor peptides and has a catalytic unit similar to that of the angiotensin I converting enzyme (ACE, kininase II, EC 3.4.15.1). 3 NEP interacts within the renin angiotensin system (RAS) cleaving angiotensin I (Ang I) and angiotensin II (Ang II) 4,5 (Figure 1). NEP's action on Ang I generates angiotensin-(1-7) [Ang-(1-7)], an heptapeptide with vasodilator activity.…”

Section: Introductionmentioning

confidence: 99%

“…The physiological effects of Ang-(1-7) are opposite to those of Ang II and would favour a blood-pressure-lowering effect under conditions of high Ang II activity. 4,5 On the other side, atrial natriuretic factor (ANF) is metabolized by NEP, an effect that could increase blood pressure. The final balance of the effects of NEP on the generation of Ang-(1-7) and metabolism of ANF contribute to determine the levels of blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

Oliveri

et al. 2004

J Hum Hypertens

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Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) ]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (Po0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (Po0.001). In normotensive DD ACE subjects, NEP activity was 0.30 7 0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (Po0.001). In the hypertensive DD ACE patients, NEP activity was 0.47 7 0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (Po0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (Po0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.

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“…Given that i) it is widely recognized that the RAS plays a role in the pathophysiology of cardiovascular and renal diseases and that under such situations, the beneficial effects of ANG-(1-7) are in opposition to the deleterious effects of ANG II [199], and ii) since the plasma concentrations of ANG-(1-7) are higher in hypertensive rats [126,189,190], it is likely that in this situation, the high plasma levels of ANG-(1-7) have an inhibitory effect on NHE3 in the proximal tubule, which should ease hypertension. Hence, the purpose of a current study in our laboratory is to clarify the direct effects of ANG-(1-7) on the NHE3 exchanger in vivo in the proximal convoluted tubules of SHR rats (hypertensives) and their controls, WKY rats (normotensives) [unpublished data].…”

Section: Actions Of Ang-(1-7) In the Kidneymentioning

confidence: 99%

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Mello-Aires¹,

Dellova²,

Castelo‐Branco³

et al. 2017

Nephrol Renal Dis

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This article reviews the main body of knowledge regarding NHE1 and NHE3 exchangers and their interaction with Angiotensin II, Angiotensin-(1-7), Aldosterone and Arginine Vasopressin, particularly their renal actions. This work addresses the biphasic effects of different hormonal doses on NHE1 or NHE3 in proximal tubule in Wistar, SHR (hypertensives) and their control WKY (normotensives) rats or MDCK cells (which share similarities with the collecting duct). The hormones were applied alone, with their inhibitors or plus agents that change the [Ca 2+ ]i. The data are compatible with hormonal stimulation of these exchangers by increases of [Ca 2+ ]i in lower range, and inhibition at high [Ca 2+ ]i. In MDCK cells and Wistar rats, low doses of ANG II, ALDO or AVP stimulated the exchangers, while high doses inhibited them. ANG-(1-7), in Wistar or WKY rats has inverse, dose-dependent effects. In SHR rats, the biphasic effects of ANG-(1-7) were similar to the effects of ANG II, ALDO or AVP in Wistar rats. The interactions between these effects may represent a mechanism that regulates extracellular volume. In hypertensives animals, a high plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated hypertension. Figure 6 shows a schematic model to describe these biphasic hormonal effects.

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Counterregulatory Actions of Angiotensin-(1-7)

Cited by 474 publications

References 53 publications

Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase

Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase

Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

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