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

• Published in: Molecular nutrition & food research 2019-05, Vol.63 (9), p.e1900063-n/a
• Main Authors: Liao, Wang, Fan, Hongbing, Davidge, Sandra T., Wu, Jianping
• Format: Article
• Language: English
• Subjects: ACE2; adults; AKT protein; Albumen; Angiotensin; Angiotensin I - metabolism; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Angiotensin-Converting Enzyme 2; animal disease models; Animals; antagonists; Antihypertensive Agents - chemistry; Antihypertensive Agents - pharmacology; antihypertensive effect; Antihypertensives; Aorta; Aorta - drug effects; Aorta - metabolism; bioactive peptides; Blood pressure; Blood Pressure - drug effects; Body weight; chemokine CCL2; Coronary vessels; Cyclooxygenase-2; Deactivation; Egg Proteins - chemistry; Egg Proteins - pharmacology; eggs; endothelial nitric oxide synthase; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Hypertension; In vivo methods and tests; inflammation; Interleukin 6; Male; males; Matrix Metalloproteinase 9 - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptides; peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Pressure effects; prostaglandin synthase; Proto-Oncogene Proteins - metabolism; rats; Rats, Inbred SHR; Receptors, G-Protein-Coupled - metabolism; Rodents; Surgical implants; Telemetry; Vasodilation; Vasodilation - drug effects
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201900063

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. ACE2/Ang (1‐7)/MasR axis is activated by an egg‐white‐ovotransferrin‐derived antihypertensive peptide IRW (Ile‐Arg‐Trp), which is responsible for lowering blood pressure in spontaneously hypertensive rats. This is the first report demonstrating the predominant role of the ACE2/Ang (1‐7)/MasR axis in having the blood‐pressuring‐lowering effect of antihypertensive peptide. This study highlights that the ACE2/Ang (1‐7)/MasR axis can be a new target for identifying novel antihypertensive peptides from food protein sources.