Chicken Muscle‐Derived ACE2‐Upregulating Peptide VVHPKESF Reduces Blood Pressure Associated with the ACE2/Ang (1‐7)/MasR Axis in Spontaneously Hypertensive Rats

SCOPE: This study aims to investigate the antihypertensive effect of four chicken muscle-derived angiotensin (Ang)-converting enzymes (ACE)-regulating peptides: Val-Arg-Pro (VRP, ACE inhibition), Leu-Lys-Tyr and Val-Arg-Tyr (LKY and VRY, ACE inhibition and ACE2 upregulation), and Val-Val-His-Pro-Lys-Glu-Ser-Phe (VVHPKESF [V-F], ACE2 upregulation) in spontaneously hypertensive rats. METHODS AND RESULTS: body weight (BW) per day, only peptide V-F significantly (p < 0.05) reduces BP, decreases circulating Ang II, and increases ACE2 and Ang (1-7) levels, and enhances aortic expressions of ACE2 and Mas receptor (MasR). Peptide V-F also attenuates vascular inflammation (TNFα, MCP-1, IL-1α, IL-15, and cyclooxygenase 2 [COX2]) and vascular oxidative stress (nitrotyrosine). The gastrointestinal (GI)-degraded fragment of peptide V-F, Val-Val-His-Pro-Lys (VVHPK), is also an ACE2-upregulating peptide. Peptides VRP, LKY, and VRY do not reduce BP, possibly due to low bioavailability or other unknown reasons. CONCLUSIONS: Peptide V-F is the first ACE2-upregulating peptide, purified and fractionated from food proteins based on in vitro ACE2 upregulation, that reduces BP associated with the activation of ACE2/Ang (1-7)/MasR axis; the N-terminal moiety VVHPK may be responsible for the antihypertensive effect of V-F.