TY - JOUR
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 - 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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U2 - 10.1002/mnfr.201900063
DO - 10.1002/mnfr.201900063
M3 - Article
C2 - 30913349
AN - SCOPUS:85064169598
SN - 1613-4125
VL - 63
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 9
M1 - 1900063
ER -