Physiological and hypotensive effects of whey protein-derived angiotensin converting enzyme inhibitory peptides in spontaneously hypertensive rats

Sustained intake of ACE inhibitory peptides derived from dietary proteins contributes to the prevention of hypertension. Peptide Arg-Leu-Ser-Asn-Pro (RLSFNP) obtained by fermentation of yogurt with Lactobacillus helveticus LB10 has been found to have ACE inhibitory capability in vitro. This study aimed to explore the effects and regulatory mechanisms of ACE inhibitory peptide RLSFNP on hypertension and gut microbiota dysbiosis in Spontaneously Hypertensive Rats (SHRs). According to the experimental results, when ACE inhibitory peptide was administered orally at different dose levels (60, 30, and 15 mg/kg BW), the systolic blood pressure of SHRs was markedly reduced. Specifically, SHR blood pressure was reduced by (21.8 +/- 1.3 mmHg) in the mid-dose group in the short-term trial. By assaying ACE content in serum and tissues, RLSFNP can rebalance the reninangiotensin system (RAS) signaling, thereby controlling blood pressure. In addition, analysis of reactive oxygen species (ROS)-related factors revealed that long-term gavage of the ACE inhibitory peptide RLSFNP affected the release of endothelial cytokines to a certain extent and effectively reduced the production of malondialdehyde (MDA). In further experiments, the ACE inhibitor RLSFNP had a potassium-preserving effect and significantly reduced the levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol. 16S rRNA results showed that the abundances of f-Ruminococcaceae-unclassified, fLachnospiraceae-unclassified, and Corynebacterium were increased by the ACE inhibitor RLSFNP in the group with the intervention of RLSFNP. There was a notable increase in specific flora in the high-dose group with Bacteroides, f-Muribaculaceae, and Ruminococcus-1. In conclusion, the ACE inhibitory peptide RLSFNP improves the renal RAS and ROS and modulates gut microbiota homeostasis, renal tissue damage, and lung injury. These findings give a solid scientific foundation for the use of whey protein-derived ACE inhibitory peptide, RLSFNP, as a potential functional food.