Abstract: Objective: This study aims to evaluate the regulatory effects of a pea oligopeptide (Val-Glu-Pro-Gln, VGPG) on diet-induced hypertension (HTN) and the underlying mechanism. Methods: The molecular docking between the oligopeptide and angiotensin-converting enzyme (ACE) was performed, and the regulatory effects of oral administration of the oligopeptide on the blood pressure, serum ACE activity, blood lipids and intestinal flora of hypertensive rats were studied. The relationship of VGPG with ACE activity and intestinal flora for the regulation of hypertension was explored. Results: The results indicated that VGPG had a notable regulatory effect on HTN and could alleviate diet-induced obesity. The underlying mechanism may be as follows: 1) through hydrogen bonding and Zn2+ coordination, VGPG combined with ACE active site to produce a competitive inhibition on ACE activity, thereby exerting a hypotensive effect; 2) by regulating the intestinal microenvironment, VGPG maintained the richness and diversity of the microbial community within the normal range, avoiding the adverse effects on blood pressure in rats associated with intestinal microbiota imbalance, and it improved the ability of intestinal bacteria to decompose carbohydrates, thus reducing the digestion and absorption of carbohydrates, controlling body mass, and finally reducing the possibility of blood pressure increase associated with overweight. VGPG with a purity of 98% at a concentration of 25 mg/mL had the best regulatory effect on hypertension without significant adverse effects on organs or the gastrointestinal environment when compared with antihypertensive drugs. Conclusion: VGPG has significant hypotensive effect on HTN. This study provides a theoretical basis for applying VGPG as a functional factor for regulating HTN and preparing relevant functional foods.

Key words: pea oligopeptides; hypertension; angiotensin converting enzyme; molecular docking; intestinal microbiota