Inhibitory effect of α(S1)- and α(S2)-casein hydrolysates on angiotensin I-converting enzyme in human endothelial cells in vitro, rat aortic tissue ex vivo, and renovascular hypertensive rats in vivo

• Published in: Journal of dairy science 2010-07, Vol.93 (7), p.2906-2921
• Main Authors: Rousseau-Ralliard, D, Goirand, F, Tardivel, S, Lucas, A, Algaron, F, Molle, D, Robert, V, Auchere, D, Boudier, J.F, Gaillard, J.L, Monnet, V, Tauzin, J, Grynberg, A
• Format: Article
• Language: English
• Subjects: alphaS1-casein; alphaS2-casein; animal models; blood pressure; casein hydrolysates; cell lines; endothelial cells; enzyme inhibition; enzyme inhibitors; experimental diets; in vitro studies; peptidyl-dipeptidase A; rats; umbilical veins
• ISSN: 0022-0302; 1525-3198
• DOI: 10.3168/jds.2010-3060

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 αS1- and αS2-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.