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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
Author(s) -
Liao Wang,
Fan Hongbing,
Davidge Sandra T.,
Wu Jianping
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900063
Subject(s) - saline , pharmacology , chemistry , blood pressure , downregulation and upregulation , medicine , endocrinology , biochemistry , gene
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.