Effect of Angiotensin-(1-7) and Bradykinin in Patients With Heart Failure Treated With an ACE Inhibitor

Davie, Andrew; McMurray, John J.V.

doi:10.1161/01.hyp.34.3.457

Cited by 57 publications

(30 citation statements)

References 35 publications

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“…However, contradictory effects of Ang-(1-7) have been reported in human vessels. While Sasaki et al (2001) reported vasodilation in the human forearm, Davie & McMurray (1999) did not observe any effect of Ang-(1-7) in the same territory in ACE inhibitor-treated patients.…”

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

confidence: 82%

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

439

369

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

confidence: 82%

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

439

369

View full text Add to dashboard Cite

show abstract

“…Furthermore, infusion of AVE (11-230 pmol/min for 60 min) in Wistar rats did not change the BP [16]. The absence of major changes in arterial pressure was expected, once chronic or acute infusion of ANG-(1-7) produces only slight alterations in MAP [9], and even high concentrations of ANG-(1-7) given by brachial arterial infusion do not cause forearm vasodilatation in patients with chronic heart failure [32]. Although effects of ANG-(1-7) on BP in vivo were still controversial, our observations suggested that the beneficial effects of AVE are due to a direct action on the heart.…”

Section: Figurementioning

confidence: 84%

Impairment of Cardiac Function and Remodeling Induced by Myocardial Infarction in Rats are Attenuated by the Nonpeptide Angiotensin‐(1–7) Analog AVE 0991

Zeng

Chen

Leng

et al. 2010

Cardiovascular Therapeutics

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SUMMARY Aims:We evaluated effects of the nonpeptide angiotensin (ANG)-(1-7) analog AVE 0991 (AVE) on cardiac function and remodeling as well as transforming growth factor-beta1 (TGF-β1)/tumor necrosis factor-alpha (TNF-α) expression in myocardial infarction rat models. Methods and Results: Sprague-Dawley rats underwent either sham surgery or coronary ligation. They were divided into four groups: sham, control, AVE, and AVE+A-779 ]-ANG-(1-7), a selective antagonist for the ANG-(1-7)] group. After 4 weeks of treatment, the AVE group displayed a significant elevation in left ventricular fractional shorting (LVFS) (25.5 ± 7.3% vs. 18.4 ± 3.3%, P < 0.05) and left ventricular ejection fraction (LVEF) (44.8 ± 7.6% vs. 32.7 ± 6.5%, P < 0.05) when compared to the control group, but no effects on the left ventricular end-diastolic and end-systolic diameters (LVDd and LVDs, respectively) were observed. In addition, we found that the myocyte diameter (18 ± 2 μm vs. 22 ± 4 μm, P < 0.05), infarct size (42.6 ± 3.6% vs. 50.9 ± 4.4%, P < 0.001) and collagen volume fraction (CVF) (16.4 ± 2.2% vs. 25.3 ± 3.2%, P < 0.001) were significantly reduced in the AVE group when compared to the control group. There were no differences in LVFS, LVEF, myocyte diameter, and infarct size between the control and AVE+A-779 groups. AVE also markedly attenuated the increased mRNA expression of collagen I (P < 0.001) and collagen III (P < 0.001) and inhibited the overexpression of TGF-β1 (P < 0.05) and TNF-α (P < 0.05) compared to the control group. Conclusion: AVE could improve cardiac function and attenuate ventricular remodeling in MI rat models. It may involve the inhibition of inflammatory factors TGF-β1/TNF-α overexpression and the action on the specific receptor Mas of ANG-(1-7).

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“…Davie and McMurray 15 recently reported that intrabrachial administration of Ang-(1-7) did not cause vasodilation and did not potentiate the vasodilator response to BK in patients with heart failure treated with an ACE inhibitor. However, in this study, pretreatment with an ACE inhibitor may have obscured any BK-potentiating effect of Ang-(1-7).…”

mentioning

confidence: 99%

Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm

et al. 2001

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Abstract-Studies in isolated vessels and rat models of hypertension suggest that angiotensin (Ang)-(1-7) potentiates the vasodilator effect of bradykinin, possibly through ACE inhibition. We therefore tested the hypothesis that Ang-(1-7) potentiates the vasodilator or tissue plasminogen activator (TPA) response to bradykinin in the human forearm vasculature. Graded doses of Ang-(1-7) (10, 100, and 300 pmol/min), bradykinin (47, 94, and 189 pmol/min), and Ang I (1, 10, and 30 pmol/min) were administered through the brachial artery to 8 normotensive subjects in random order. Thirty minutes after initiation of a constant infusion of Ang-(1-7) (100 pmol/min), bradykinin and Ang I infusions were repeated. There were no systemic hemodynamic effects of the agonists. Bradykinin significantly increased forearm blood flow (PϽ0.001, from 3.8Ϯ0.5 to 13.9Ϯ3.1 mL/min per 100 mL at 189 pmol/min) and net TPA release (Pϭ0.007, from 1.1Ϯ1.0 to 23.6Ϯ6.2 ng/min per 100 mL at 189 pmol/min), whereas Ang I caused vasoconstriction (Pϭ0.003, from 3.3Ϯ0.4 to 2.5Ϯ0.3 mL/min per 100 mL at 30-pmol/min dose). There was no effect of Ang-(1-7) on either forearm blood flow (Pϭ0.62, 3.3Ϯ0.4 to 3.5Ϯ0.4 mL/min per 100 mL at 300 pmol/min) or TPA release (Pϭ0.52, from 0.7Ϯ0.8 to 1.0Ϯ0.7 ng/min/100 mL at 300 pmol/min). Moreover, there was no effect of 100 pmol/min Ang-( A ngiotensin (Ang)-(1-7) is formed from Ang I by the action of the endopeptidase neprilysin (EC 3.4.24.11) and degraded to Ang-(1-5) by ACE. 1 Ang-(1-7) concentrations may be increased during ACE inhibition. 2,3 In vitro and in animal models, Ang-(1-7) acts as a vasodilator and exhibits antiproliferative effects. 4 -6 For example, in isolated canine, porcine, and human arteries, Ang-(1-7) causes nitric oxidedependent vasodilation. 4,5,7,8 Significantly, the vasodilator effect of Ang-(1-7) can be blocked by bradykinin (BK) receptor antagonism. 4,5,7 This finding and the observation that Ang-(1-7) enhances the hypotensive effect of BK in rats as well as isolated arteries 5,9 -11 suggest the hypothesis that Ang-(1-7) causes vasodilation by potentiating the effects of BK. Ang-(1-7), an ACE substrate cleaved by the N-domain active site, acts as an inhibitor of the C-domain active site of the enzyme 12 and thus may potentiate BK by blocking its degradation. Ang-(1-7) also may potentiate the actions of BK by resensitizing its receptor. 13 In addition, studies in human coronary arteries 8 and rabbit aortic rings 14 suggest that Ang-(1-7) may antagonize angiotensin-mediated vasoconstriction through effects at the AT 1 receptor.The interaction between Ang-(1-7) and BK has not been studied extensively in humans. Davie and McMurray 15 recently reported that intrabrachial administration of Ang-(1-7) did not cause vasodilation and did not potentiate the vasodilator response to BK in patients with heart failure treated with an ACE inhibitor. However, in this study, pretreatment with an ACE inhibitor may have obscured any BK-potentiating effect of Ang-(1-7). In addition, no studies have reported whe...

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Effect of Angiotensin-(1-7) and Bradykinin in Patients With Heart Failure Treated With an ACE Inhibitor

Cited by 57 publications

References 35 publications

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

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

Impairment of Cardiac Function and Remodeling Induced by Myocardial Infarction in Rats are Attenuated by the Nonpeptide Angiotensin‐(1–7) Analog AVE 0991

Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm

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