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

• Published in: Molecular nutrition & food research 2024-03, Vol.68 (5), p.e2300524-n/a
• Main Authors: Fan, Hongbing, Shang, Nan, Davidge, Sandra T., Wu, Jianping
• Format: Article
• Language: English
• Subjects: ACE2; Ang (1‐7); Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensin-Converting Enzyme 2 - pharmacology; Animals; Antihypertensive Agents - pharmacology; Antihypertensives; Aorta; bioactive peptides; Bioavailability; Blood Pressure; Body weight; chicken; Chickens; Chickens - metabolism; Cyclooxygenase-2; Hypertension; inflammation; Muscles - metabolism; Nitrotyrosine; Oral administration; Oxidative stress; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptides; Peptides - pharmacology; Peptidyl-Dipeptidase A - metabolism; Rats; Rats, Inbred SHR; spontaneously hypertensive rat; Telemetry; Up-regulation
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202300524

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 Rats (12–14 weeks old) are grouped: 1) untreated, 2) VRP, 3) LKY, 4) VRY, and 5) V‐F. Blood pressure (BP) is monitored using implantable telemetry technology. Over 18‐day oral administration of 15 mg kg−1 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. A chicken muscle‐derived ACE2‐upregulating peptide, VVHPKESF, lowers blood pressure in spontaneously hypertensive rats over 18‐day oral administration (15 mg kg−1 body weight per day). The peptide reduces blood pressure by mitigating oxidative stress and inflammatory responses (TNFα, MCP‐1, IL‐1α, IL‐15, and COX2) and activating the ACE2/Ang (1‐7)/MasR axis. The N‐terminal moiety VVHPK may be responsible for the antihypertensive effect of peptide VVHPKESF.