The antihypertensive activity of two αs1-casein-derived peptides and casein hydrolysate containing these sequences was evaluated in the presence of naloxone. The activity was abolished by this opioid antagonist at 2, 4, and 6 h post-administration. Similarly, the antihypertensive effect of the αs1-casein peptides 90RYLGY94 (-23.8 ± 2.5 mmHg) and 143AYFYPEL149 (-21.1 ± 3.2 mmHg) at 5 mg/kg of body weight was antagonized by the co-administration of naloxone. Because peptide 143AYFYPEL149 had recently shown opioid activity, a molecular dynamic simulation of this peptide with human μ-opioid receptor was performed to demonstrate its favorable structure and interaction energy, despite the presence of Ala at the N terminus. Altogether, these results revealed that the in vivo effect on systolic blood pressure of the studied αs1-casein peptides is mediated by interaction with opioid receptors and the antihypertensive activity of casein hydrolysate can be very likely ascribed to them with the possible contribution of other mechanisms.
Keywords: antihypertensive peptide; casein hydrolysate; naloxone; opioid receptor; spontaneously hypertensive rat.