Implication of Opioid Receptors in the Antihypertensive Effect of a Novel Chicken Foot-Derived Peptide

The peptide AVFQHNCQE demonstrated to produce nitric oxide-mediated antihypertensive effect. This study investigates the bioavailability and the opioid-like activity of this peptide after its oral administration. For this purpose, in silico and in vitro approaches were used to study the peptide susceptibility to GI digestion. In addition, AVFQHNCQE absorption was studied both in vitro by using Caco-2 cell monolayers and in vivo evaluating peptide presence in plasma from Wistar rats by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Both in vivo and in vitro experiments demonstrated that peptide AVFQHNCQE was not absorbed. Thus, the potential involvement of opioid receptors in the BP-lowering effect of AVFQHNCQE was studied in the presence of opioid receptors-antagonist Naloxone. No changes in blood pressure were recorded in rats administered Naloxone, demonstrating that AVFQHNCQE antihypertensive effect is mediated through its interaction with opioid receptors. AVFQHNCQE opioid-like activity would clarify the antihypertensive properties of AVFQHNCQE despite its lack of absorption.