Egg White–Derived Antihypertensive Peptide IRW (Ile-Arg-Trp) Reduces Blood Pressure in Spontaneously Hypertensive Rats via the ACE2/Ang (1-7)/Mas Receptor Axis

Wang Liao; Hongbing Fan; Sandra T. Davidge; Jianping Wu

doi:10.1002/mnfr.201900063

Egg White–Derived Antihypertensive Peptide IRW (Ile-Arg-Trp) Reduces Blood Pressure in Spontaneously Hypertensive Rats via the ACE2/Ang (1-7)/Mas Receptor Axis

Wang Liao, Hongbing Fan, Sandra T. Davidge, Jianping Wu

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

Scope: It is found in the previous study that egg-white-derived antihypertensive peptide Ile-Arg-Trp (IRW) upregulated angiotensin converting enzyme 2 (ACE2) in spontaneously hypertensive rats (SHRs). The objective of this study is to evaluate the contribution of ACE2 activation by IRW to blood-pressure-lowering activity in vivo. Methods and results: Adult male SHRs (13–15 week old) are assigned into four groups: 1) untreated with saline infusion; 2) IRW administration (15 mg per kg body weight) with saline infusion; 3) Mas receptor (MasR) antagonist A779 (48 µg per kg body weight per h) infusion; 4) A779 infusion and IRW. Animals are implanted with telemetry transmitter first, and then an osmotic pump filled with saline or A779 is implanted. A779/saline is infused for 7 days, continued with an additional 7 days of treatments. Results indicate that blocking MasR abolished the blood-pressure-lowering effect of IRW. Akt/eNOS signaling in aorta is upregulated by IRW treatment but deactivated by A779 infusion. Circulating levels of interleukin 6 and monocyte chemoattractant protein 1, along with cyclooxygenase 2 in aorta are reduced by IRW but restored by A779 infusion. Conclusion: IRW reduces blood pressure of SHR via the ACE2/Ang (1-7)/MasR axis. Mechanisms pertaining to IRW as an ACE2 activator in vivo include enhanced endothelium-dependent vasorelaxation and reduced vascular inflammation.

Original language	English
Article number	1900063
Journal	Molecular Nutrition and Food Research
Volume	63
Issue number	9
DOIs	https://doi.org/10.1002/mnfr.201900063
State	Published - May 2019

Bibliographical note

Funding Information:
The authors would like to acknowledge Mrs. Sareh Panahi for providing technical support in doing animal surgery. This research was funded by a grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to J.W. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. S.T.D. is a Canada Research Chair in Maternal and Perinatal Cardiovascular Health. W.L. designed and performed the experiments, and wrote the manuscript; H.F. performed the experiments and analyzed the data; S.T.D. and J.W. designed the experiments.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

ACE2
bioactive peptides
blood pressure
hypertension

ASJC Scopus subject areas

Biotechnology
Food Science

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10.1002/mnfr.201900063

Cite this

@article{3e0edd1690db4e2bb1977185012d383c,

title = "Egg White–Derived Antihypertensive Peptide IRW (Ile-Arg-Trp) Reduces Blood Pressure in Spontaneously Hypertensive Rats via the ACE2/Ang (1-7)/Mas Receptor Axis",

abstract = "Scope: It is found in the previous study that egg-white-derived antihypertensive peptide Ile-Arg-Trp (IRW) upregulated angiotensin converting enzyme 2 (ACE2) in spontaneously hypertensive rats (SHRs). The objective of this study is to evaluate the contribution of ACE2 activation by IRW to blood-pressure-lowering activity in vivo. Methods and results: Adult male SHRs (13–15 week old) are assigned into four groups: 1) untreated with saline infusion; 2) IRW administration (15 mg per kg body weight) with saline infusion; 3) Mas receptor (MasR) antagonist A779 (48 µg per kg body weight per h) infusion; 4) A779 infusion and IRW. Animals are implanted with telemetry transmitter first, and then an osmotic pump filled with saline or A779 is implanted. A779/saline is infused for 7 days, continued with an additional 7 days of treatments. Results indicate that blocking MasR abolished the blood-pressure-lowering effect of IRW. Akt/eNOS signaling in aorta is upregulated by IRW treatment but deactivated by A779 infusion. Circulating levels of interleukin 6 and monocyte chemoattractant protein 1, along with cyclooxygenase 2 in aorta are reduced by IRW but restored by A779 infusion. Conclusion: IRW reduces blood pressure of SHR via the ACE2/Ang (1-7)/MasR axis. Mechanisms pertaining to IRW as an ACE2 activator in vivo include enhanced endothelium-dependent vasorelaxation and reduced vascular inflammation.",

keywords = "ACE2, bioactive peptides, blood pressure, hypertension",

author = "Wang Liao and Hongbing Fan and Davidge, {Sandra T.} and Jianping Wu",

note = "Funding Information: The authors would like to acknowledge Mrs. Sareh Panahi for providing technical support in doing animal surgery. This research was funded by a grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to J.W. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. S.T.D. is a Canada Research Chair in Maternal and Perinatal Cardiovascular Health. W.L. designed and performed the experiments, and wrote the manuscript; H.F. performed the experiments and analyzed the data; S.T.D. and J.W. designed the experiments. Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2019",

month = may,

doi = "10.1002/mnfr.201900063",

language = "English",

volume = "63",

number = "9",

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T1 - Egg White–Derived Antihypertensive Peptide IRW (Ile-Arg-Trp) Reduces Blood Pressure in Spontaneously Hypertensive Rats via the ACE2/Ang (1-7)/Mas Receptor Axis

AU - Liao, Wang

AU - Fan, Hongbing

AU - Davidge, Sandra T.

AU - Wu, Jianping

N1 - Funding Information: The authors would like to acknowledge Mrs. Sareh Panahi for providing technical support in doing animal surgery. This research was funded by a grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to J.W. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. S.T.D. is a Canada Research Chair in Maternal and Perinatal Cardiovascular Health. W.L. designed and performed the experiments, and wrote the manuscript; H.F. performed the experiments and analyzed the data; S.T.D. and J.W. designed the experiments. Publisher Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/5

Y1 - 2019/5

N2 - Scope: It is found in the previous study that egg-white-derived antihypertensive peptide Ile-Arg-Trp (IRW) upregulated angiotensin converting enzyme 2 (ACE2) in spontaneously hypertensive rats (SHRs). The objective of this study is to evaluate the contribution of ACE2 activation by IRW to blood-pressure-lowering activity in vivo. Methods and results: Adult male SHRs (13–15 week old) are assigned into four groups: 1) untreated with saline infusion; 2) IRW administration (15 mg per kg body weight) with saline infusion; 3) Mas receptor (MasR) antagonist A779 (48 µg per kg body weight per h) infusion; 4) A779 infusion and IRW. Animals are implanted with telemetry transmitter first, and then an osmotic pump filled with saline or A779 is implanted. A779/saline is infused for 7 days, continued with an additional 7 days of treatments. Results indicate that blocking MasR abolished the blood-pressure-lowering effect of IRW. Akt/eNOS signaling in aorta is upregulated by IRW treatment but deactivated by A779 infusion. Circulating levels of interleukin 6 and monocyte chemoattractant protein 1, along with cyclooxygenase 2 in aorta are reduced by IRW but restored by A779 infusion. Conclusion: IRW reduces blood pressure of SHR via the ACE2/Ang (1-7)/MasR axis. Mechanisms pertaining to IRW as an ACE2 activator in vivo include enhanced endothelium-dependent vasorelaxation and reduced vascular inflammation.

AB - Scope: It is found in the previous study that egg-white-derived antihypertensive peptide Ile-Arg-Trp (IRW) upregulated angiotensin converting enzyme 2 (ACE2) in spontaneously hypertensive rats (SHRs). The objective of this study is to evaluate the contribution of ACE2 activation by IRW to blood-pressure-lowering activity in vivo. Methods and results: Adult male SHRs (13–15 week old) are assigned into four groups: 1) untreated with saline infusion; 2) IRW administration (15 mg per kg body weight) with saline infusion; 3) Mas receptor (MasR) antagonist A779 (48 µg per kg body weight per h) infusion; 4) A779 infusion and IRW. Animals are implanted with telemetry transmitter first, and then an osmotic pump filled with saline or A779 is implanted. A779/saline is infused for 7 days, continued with an additional 7 days of treatments. Results indicate that blocking MasR abolished the blood-pressure-lowering effect of IRW. Akt/eNOS signaling in aorta is upregulated by IRW treatment but deactivated by A779 infusion. Circulating levels of interleukin 6 and monocyte chemoattractant protein 1, along with cyclooxygenase 2 in aorta are reduced by IRW but restored by A779 infusion. Conclusion: IRW reduces blood pressure of SHR via the ACE2/Ang (1-7)/MasR axis. Mechanisms pertaining to IRW as an ACE2 activator in vivo include enhanced endothelium-dependent vasorelaxation and reduced vascular inflammation.

KW - ACE2

KW - bioactive peptides

KW - blood pressure

KW - hypertension

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Egg White–Derived Antihypertensive Peptide IRW (Ile-Arg-Trp) Reduces Blood Pressure in Spontaneously Hypertensive Rats via the ACE2/Ang (1-7)/Mas Receptor Axis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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