Angiotensin-(1-7) Induces Bradykinin-Mediated Hypotensive Responses in Anesthetized Rats

Abbas, Asad; Gorelik, Gabriela; Carbini, Luis A.; Scicli, A. G.

doi:10.1161/01.hyp.30.2.217

Cited by 67 publications

(73 citation statements)

References 17 publications

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“…This explains why Ang II receptor blockers were inactive, but a B 2 receptor blocker abolished Ang-(1-7) effects. 9,14 It also follows that ACE inhibitors may block some of the activity of Ang-(1-7) by similar effects and competing for ACE. 9,29,30 Because of the differences in the cleavage of biological substrates by the two domains, it would be important to develop a second generation of ACE inhibitors that react mainly with one of the active sites of ACE.…”

Section: Discussionmentioning

confidence: 99%

“…9,13 This vasodilation and hypotension by Ang-(1-7) were also abolished by the BK B 2 receptor antagonist HOE 140. 14 In addition, Ang-(1-7) inhibits purified canine ACE. 9 It is hypothesized that Ang-(1-7) is synergistic with BK because it either has a different Ang receptor subtype, is a ligand for the B 2 receptor, or inhibits the enzymatic inactivation of BK.…”

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confidence: 99%

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N-Domain–Specific Substrate and C-Domain Inhibitors of Angiotensin-Converting Enzyme

et al. 1998

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Abstract-We used the isolated N-and C-domains of the angiotensin I-converting enzyme (N-ACE and C-ACE; ACE; kininase II) to investigate the hydrolysis of the active 1-7 derivative of angiotensin (Ang) II and inhibition by 5-S-5-benzamido-4-oxo-6-phenylhexanoyl-L-proline (keto-ACE). Ang-(1-7) is both a substrate and an inhibitor; it is cleaved by N-ACE at approximately one half the rate of bradykinin but negligibly by C-ACE. It inhibits C-ACE, however, at an order of magnitude lower concentration than N-ACE; the IC 50 of C-ACE with 100 mol/L Ang I substrate was 1.2 mol/L and the K i was 0.13. While searching for a specific inhibitor of a single active site of ACE, we found that keto-ACE inhibited bradykinin and Ang I hydrolysis by C-ACE in approximately a 38-to 47-times lower concentration than by N-ACE; IC 50 values with C-ACE were 0.5 and 0.04 mol/L. Furthermore, we investigated how Ang-(1-7) acts via bradykinin and the involvement of its B 2 receptor. Ang-(1-7) was ineffective directly on the human bradykinin B 2 receptor transfected and expressed in Chinese hamster ovary cells. However, Ang-(1-7) potentiated arachidonic acid release by an ACE-resistant bradykinin analogue (1 mol/L), acting on the B 2 receptor when the cells were cotransfected with cDNAs of both B 2 receptor and ACE and the proteins were expressed on the plasma membrane of Chinese hamster ovary cells. Thus like other ACE inhibitors, Ang-(1-7) can potentiate the actions of a ligand of the B 2 receptor indirectly by binding to the active site of ACE and independent of blocking ligand hydrolysis. This potentiation of kinins at the receptor level can explain some of the well-documented kininlike actions of Ang-(1-7).(Hypertension. 1998;31:912-917.)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

N-Domain–Specific Substrate and C-Domain Inhibitors of Angiotensin-Converting Enzyme

et al. 1998

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“…On the other hand, interaction of Ang (1-7) with bradykinin has emerged as an endogenous antihypertensive/antitrophic mechanism, opposing many of the effects of Ang II that are mediated by AT1 (80,81,83). Ang (1-7) acting via its receptor Mas (different from AT 1 or AT 2 ) induced bradykinin-mediated hypotension in SHR and normal rats (93) as well as dilatation of porcine coronary arteries (4,31). Cleavage of Ang I and II to Ang (1-7) by various endopeptidases (60,61) is another way kinins could expand the beneficial effects of ACE inhibitors or ARBs.…”

Section: Role Of Kinins In the Cardioprotective Effect Of Angiotensinmentioning

confidence: 99%

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

Carretero¹,

Yang²,

Rhaleb³

2005

Hypertension

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“…42,44 Indeed, when used at high concentrations, Ang-(1-7) can produce Ang II-like effects. 15,45 These actions can be explained by low affinity binding of Ang-(1-7) to AT 1 receptors. 38 Alternatively, Ang-(1-7), binding to its specific receptors and/or to AT 1 receptors, can interfere with extracellular Ca 2ϩ influx into smooth muscle cells, as recently proposed for mesangial cells.…”

Section: Interactions Of Ang-(1-7) With Ang II In Blood Vesselsmentioning

confidence: 99%

“…1 Evidence that Ang-(1-7) actions can be kinin mediated has been obtained with several preparations. 8,9,[13][14][15] In all studies aiming at clarifying the contribution of kinins to the action of Ang-(1-7), the BK-B 2 antagonist HOE 140 was used. This approach does not rule out the possibility that Ang-(1-7) could be acting by potentiating endogenous kinins or by a cross-talk mechanism dependent on unoccupied BK-B 2 receptors.…”

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Interactions Between Angiotensin-(1-7), Kinins, and Angiotensin II in Kidney and Blood Vessels

Santos

Passaglio²,

Pesquero³

et al. 2001

Hypertension

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Abstract-The heptapeptide angiotensin (Ang)-(1-7) is currently considered one of the biologically active end products of the renin-angiotensin system. The formation of Ang-(1-7) by pathways independent of Ang II generation, the selectivity of its actions, and its peculiar property of exhibiting effects that are partially opposite of those of the parent compound, Ang II, confer a unique biochemical and functional profile to this peptide. In this article, we will review novel aspects of the biological actions of Ang-(1-7), dealing with its interaction with Ang II and kinins, especially in the kidney and blood vessels. Key Words: bradykinin Ⅲ renin-angiotensin system Ⅲ receptors, angiotensin T he heptapeptide angiotensin (Ang)-(1-7) is formed from Ang I and Ang II by tissue peptidases, including neutral endopeptidase (neprilysin), thimet oligopeptidase, prolylcarboxypeptidase, and prolyl-endopeptidase. 1 In addition, the possibility should be considered that at least in the kidney and heart, Ang-(1-7) could be formed from Ang I or Ang II by a pathway involving the ACE-related enzyme ACE2 2,3 ( Figure 1). Once formed, Ang-(1-7) is rapidly hydrolyzed, especially by ACE. 4 Therefore, in the presence of ACE inhibition, the levels of Ang-(1-7), which circulates in blood at concentrations close to those of Ang II, raises several-fold, 5 probably owing to both the increase in Ang I concentration and the decrease in Ang-(1-7) breakdown. The related observation that Ang-(1-7) can increase following long-term administration of angiotensin type 1 (AT 1 ) receptor blockers 1 raises the possibility that Ang-(1-7) contributes to the pharmacological effects of both ACE inhibitors and AT 1 receptor antagonists. Interactions between Ang-(1-7) and Kinins in Blood VesselsMost of the interactions between Ang-(1-7) and bradykinin (BK) have been reported to occur in blood vessels. 1,6 -11 There are 2 major types of interaction: potentiation of BK by Ang-(1-7) and mediation of the vascular actions of Ang-(1-7) by kinins, although the latter does not exclude the former. Potentiation of BK by Ang-(1-7) has been observed in conscious normotensive and hypertensive rats in terms of the BK hypotensive effect in the whole animal 1,6 or the vasodilating action of BK in rat mesenteric microvessels in situ. 1,7 Brosnihan and colleagues 8,9 have shown that preincubation of isolated dog coronary arteries with Ang-(1-7) increased the relaxation produced by BK. Similarly, Almeida et al 10 have shown that Ang-(1-7) at 2 nmol/L concentration increased the vasodilation produced by BK in isolated rat hearts. Interestingly, the venoconstriction produced by BK in rabbit endothelium denuded femoral vein was also potentiated by Ang-(1-7), 11 indicating that the BK potentiating activity of Ang- (1-7) is not an exclusively endothelium-dependent phenomenon. Potentiation of bradykinin by Ang-(1-7) has also been described in other preparations. In Chinese hamster ovary cells co-transfected with the human cDNA for BK-B 2 receptors and ACE, Deddish et al 12 descri...

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Angiotensin-(1-7) Induces Bradykinin-Mediated Hypotensive Responses in Anesthetized Rats

Cited by 67 publications

References 17 publications

N-Domain–Specific Substrate and C-Domain Inhibitors of Angiotensin-Converting Enzyme

N-Domain–Specific Substrate and C-Domain Inhibitors of Angiotensin-Converting Enzyme

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

Interactions Between Angiotensin-(1-7), Kinins, and Angiotensin II in Kidney and Blood Vessels

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