Potentiation of Bradykinin by Angiotensin-(1-7) on Arterioles of Spontaneously Hypertensive Rats Studied In Vivo

Federal University of Minas Gerais, Cidade de Minas, Minas Gerais, Brazil
Hypertension (Impact Factor: 6.48). 03/2001; 37(2 Part 2):703-9. DOI: 10.1161/01.HYP.37.2.703
Source: PubMed


In the present study, we investigated the potentiating effect of angiotensin-(1-7) [Ang-(1-7)] on bradykinin (BK)-induced vasodilation in the mesenteric vascular bed of anesthetized spontaneously hypertensive rats using intravital microscopy. Topical application of BK and Ang-(1-7) induced vasodilation in mesenteric arterioles. The BK-induced effect, but not acetylcholine, sodium nitroprusside, or histamine responses, was potentiated in the presence of Ang-(1-7). This interaction was abolished by BK-B(2) and Ang-(1-7) antagonists (HOE 140 and A-779, respectively), a K(+) channel blocker (tetraethylammonium), and cyclooxygenase inhibitors (indomethacin and diclofenac); however, nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester) did not modify the Ang-(1-7)-potentiating activity. Long-term angiotensin-converting enzyme (ACE) inhibition increased BK and Ang-(1-7)-induced vasodilation. The BK potentiation by Ang-(1-7) was preserved after ACE inhibition, Ang II type 1 receptor blockade, or the combination of both treatments. The most striking finding of this study was the unexpected observation that the potentiation of BK vasodilation in spontaneously hypertensive rats treated short- or long-term with ACE inhibitors was reverted by the Ang-(1-7) antagonist A-779. Our results unmasked a key role for an Ang-(1-7)-related mechanism in mediating BK potentiation by ACE inhibitors.

Download full-text


Available from: Robson Santos
  • Source
    • "Our analysis suggests that these two receptors may show binding affinity for the ligands of both angiotensin type and bradykinin receptors. Our results confirm the earlier finding where bradykinin receptors were shown to respond to angiotensin-(1–7) [Ang-(1–7)] (Fernandes et al., 2001) (Fig. 7). Cluster 7 consists of LT4R2/BLT2 and LT4R1/BLT1 receptors. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Current methods of G protein coupled receptors (GPCRs) phylogenetic classification are sequence based and therefore inappropriate for highly divergent sequences, sharing low sequence identity. In this study, sequence structure profile based alignment generated by PROMALS3D was used to understand the GPCR Class A Rhodopsin superfamily evolution using the MEGA 5 software. Phylogenetic analysis included a combination of Neighbor joining method and Maximum Likelihood method, with1000 bootstrap replicates. Our study is able to identify potential ligand association for class A Orphans /Putative/unclassified Class A receptors with no cognate ligand information: GPR21 and GPR52 with fatty acids; GPR75 with Neuropeptide Y; GPR82,GPR18, GPR141 with N-arachidonylglycine; GPR176 with Free fatty acids, GPR10 with Tachykinin & Neuropeptide Y; GPR85 with ATP,ADP&UDPglucose; GPR151 with Galanin; GPR153 and GPR162 with Adrenalin, noradrenalin; GPR146,GPR139, GPR142 with Neuromedin, Ghrelin, Neuromedin U-25 & thyrotropin-releasing hormone; GPR171 with ATP,ADP & UDP Glucose; GPR88, GPR135,GPR161,GPR101with 11-cis-retinal; GPR83 with Tackykinin; GPR148 with Prostanoids, GPR109b,GPR81,GPR31with ATP &UTP, GPR150 with GnRH I & GnRH I. Furthermore, we suggest that this study would prove useful in re classification of receptors, selecting templates for homology modeling and identifying ligands which may show cross reactivity with other GPCRs as signaling via multiple ligands play a significant role in disease modulation.
    Full-text · Article · May 2014 · Molecular Phylogenetics and Evolution
  • Source
    • "Interestingly, they preserve endothelial function in vitro11 and potentiate on bradykinin and angiotensin-(1-7) [Ang-(1-7)] induced vasodilatation.18 Bradykinin and Ang-(1-7) are physiological vasodilators believed to have some interaction with each other via the ACE-2-Mas-receptor axis.19,20 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1) has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC) have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature. We focused on the cis/trans configurations of the peptide bonds in proline-containing tripeptides in order to discover whether the different structural properties of these peptides influence their activity in ACE-1 inhibition. We hypothesized that the configuration of proline-containing peptides plays a significant role in enzyme inhibition. AutoDock 4.2 docking software was used to predict suitable peptide bond configurations of the tripeptides. Besides modeling studies, we completed ACE-1 activity measurements in vitro using HUVEC cultures. In HUVEC cells, both IPP and VPP inhibited ACE-1. Based on molecular docking studies, we propose that in ACE-1 inhibition IPP and VPP share a similar cis configuration between the first aliphatic (isoleucine or valine) and the second (proline) amino acid residues and more different configurations between two proline residues. In vivo experiments are needed to validate the significance of the present findings.
    Full-text · Article · Feb 2014 · Targets & therapy
  • Source
    • "Furthermore, Benter et al.'s work would suggest that Ang-(1-7) might oppose the haemodynamic actions of Ang II. Another peptide contributing to the vasodilatory effects of Ang-(1-7) is bradykinin (BK) [29], a molecule Ang-(1-7) is shown to interact with. Paula and colleagues [30] suggested that Ang-(1-7) potentiates the hypotensive effect of bradykinin in vivo and prostaglandins may participate in the mechanism of potentiation by Ang-(1-7). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Context. Heart failure (HF) is a common condition causing much morbidity and mortality despite major advances in pharmacological and device therapies. Preclinical data suggest a cardioprotective role of Angiotensin-(1-7) in animal models of HF. Objective. Perform a systematic review on the effects of Angiotensin-(1-7) on humans, focusing on HF. Results. 39 studies were included in the review (4 in human HF and (35) in non-HF patients). There is only one intervention study on 8 patients with human HF, using Angiotensin-(1-7), with forearm blood flow (FBF) as the endpoint. Angiotensin-(1-7) caused no significant effect on FBF in this HF study but caused vasodilation in 3 out of 4 non-HF studies. In one other non-HF study, Angiotensin-(1-7) infusion led to a significant increase in blood pressure in normal men; however, effects were <0.03% that of angiotensin II. Cardioprotective effects seen in non-HF studies include for instance beneficial actions against atherosclerosis and myocardial fibrosis. Conclusions. The main finding of our systematic review is that Angiotensin-(1-7) plays an important cardioprotective role in HF in animals and in patients without heart failure. More research is required to test the hypothesis that Angiotensin-(1-7) benefits patients with heart failure.
    Full-text · Article · Dec 2013 · International Journal of Peptides
Show more