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

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.