Inhibitory effect of αS1- and αS2-casein hydrolysates on angiotensin I-converting enzyme in human endothelial cells in vitro, rat aortic tissue ex vivo, and renovascular hypertensive rats in vivo

Abstract

A great number of milk-derived peptides have been shown to exhibit angiotensin converting enzyme (ACE) inhibitory properties and thus potential utility in the regulation of blood pressure. The present work aimed to investigate the effects of 2 milk trypsin hydrolysates from alpha(S1)- and alpha(S2)-casein (CH1 and CH2, respectively) on ACE activity evaluated in human umbilical vein endothelial cells (HUVEC) in vitro, rat aortic tissues ex vivo, and renovascular hypertensive rat in vivo. Incubation of HUVEC and rat aortic tissues with CH1 or CH2 induced a concentration-dependent inhibition of hydrolysis of the ACE substrate hippuryl-histidyl-leucine (HHL), the hydrolysates being much less potent than perindopril (an ACE inhibitor). However, in contrast to perindopril, CH1 and CH2 failed to modify angiotensin I-induced aortic ring vasoconstriction. The HPLC profiles of rat plasma after intragastric administration were variable among individuals but none of the observed peaks corresponded to peptides comprising CH1 or CH2 or to fragments of these peptides. During 4 wk of cardiovascular monitoring, in hydrolysate-fed renovascular hypertensive rats, systolic blood pressure weakly decreased compared with the control group. However, the CH1-fed hypertensive rats exhibited a decrease of heart rate during the nocturnal period of activity. To conclude, our results show that CH1 and CH2 inhibited ACE activity in HUVEC and rat aortic tissue but failed to antagonize the aortic-constricting effects of the natural agonist angiotensin I. Moreover, we demonstrated that CH1, to a greater extent than CH2, can slightly affect cardiovascular parameters although the ingested bioactive peptides could not be detected in the blood.

Functional and potential therapeutic ACE-inhibitory peptides derived from bromelain hydrolysis of trevally proteins

“…These results are similar to those published in the literature on ACE-inhibitory activity of food protein hydrolysates (Guo, 2009; Nakajima, Yoshie-Stark, & Ogushi, 2009;Raghavan & Kristinsson, 2009;Rousseau-Ralliard et al, 2010;Tomatsu et al, 2013;Zhao et al, 2009). The IC50 values of trevally protein hydrolysates were quite low ranging from 1.99 to 3.34 mg/mL for hydrolysates from soluble protein substrate and from 2.45 to 4.74 mg/mL for hydrolysates from insoluble protein substrate.…”

Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar) Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

“…During in vitro studies of peptides with the sequences: TVY, VFPS, VTVNPYKLWLP, YALPHA and ALPHA, they were recognized as ACE inhibitors [18,19,20,21,22,23]. Peptides with the sequences: IVY, VW, IY, IW, VY and IWHHT were experimentally recognized as antihypertensive i.e.…”

Molecular Mechanisms Associated with Angiotensin-Converting Enzyme-Inhibitory Peptide Activity on Vascular Extracellular Matrix Remodeling

“…It is purified Leu-Arg-Pro-Val-Ala-Ala from bovine lactoferrin, which possesses several physiological functions, such as inflammatory response modulation, immune system activation and myelopoiesis control. Previous studies demonstrated that LAP possess antihypertensive activity and improves vascular remodeling [2,3,4,5]. However, it was unclear whether or not it interferes with ECM production and degradation in vascular remodeling.…”

“…Inhibiting ACE decreases AngII, which is currently one of the most efficient tools used to control hypertension and reverse vascular remodeling. Synthetic ACE inhibitors (ACEI) have been widely used since they may reverse vascular remodeling, but they also have some side effects [2,3,4,5]. …”