Evidence that Nitric Oxide is Involved in the Blood Pressure Lowering Effect of the Peptide AVFQHNCQE in Spontaneously Hypertensive Rats

Abstract

AVFQHNCQE is an antihypertensive nonapeptide obtained from a chicken foot protein hydrolysate. The present study aims to investigate the mechanisms involved in its blood pressure (BP)-lowering effect. Male (17–20 weeks old) spontaneously hypertensive rats (SHR) were used in this study. Rats were divided into two groups and orally administered water or 10 mg/kg body weight (bw) AVFQHNCQE. One hour post-administration, animals of both groups were intra-peritoneally treated with 1 mL of saline or with 1 mL of saline containing 30 mg/kg bw Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, or with 1 mL of saline containing 5 mg/kg bw indomethacin, which is an inhibitor of prostacyclin synthesis (n = 6 per group). Systolic BP was recorded before oral administration and six hours after oral administration. In an additional experiment, SHR were administered water or 10 mg/kg bw AVFQHNCQE (n = 6 per group) and sacrificed six hours post-administration to study the mechanisms underlying the peptide anti-hypertensive effect. Moreover, the relaxation caused by AVFQHNCQE in isolated aortic rings from Sprague-Dawley rats was evaluated. The BP-lowering effect of the peptide was not changed after indomethacin administration but was completely abolished by L-NAME, which demonstrates that its anti-hypertensive effect is mediated by changes in endothelium-derived NO availability. In addition, AVFQHNCQE administration downregulated aortic gene expression of the vasoconstrictor factor endothelin-1 and the endothelial major free radical producer NADPH. Moreover, while no changes in plasma ACE activity were observed after its administration, liver GSH levels were higher in the peptide-treated group than in the water group, which demonstrates that AVFQHNCQE presents antioxidant properties.

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

“…In this sense, it has been demonstrated that the hydrolysis of chicken foot proteins is a good strategy for the obtaining of bioactive peptides able to reduce BP [ 22 , 24 ]. The NO-mediated antihypertensive effect of the peptide AVFQHNCQE (10 mg/kg bw), identified initially in the chicken foot hydrolysate Hpp11, has been previously demonstrated in SHR [ 22 , 23 ]. Nevertheless, it is unknown if this peptide sequence is susceptible to GI digestion, resulting in new peptide fragments which might be the responsibility of AVFQHNCQE bioactivity.…”

“…The mechanism of action proposed driven by the stimulation of these opioid receptors is the subsequent NO release causing vasodilation [ 30 , 31 , 32 , 33 ]. Therefore, considering that AVFQHNCQE was not absorbed and its antihypertensive effect was mediated by NO [ 23 ], it was investigated the participation of opioid receptors in its effect on blood pressure. Thus, the antihypertensive properties of AVFQHNCQE were studied in presence of Naloxone, which is an opioid receptor antagonist [ 34 ].…”

“…AVFQHNCQE is a nonapeptide initially identify in the chicken foot hydrolysate Hpp11, which exhibited antihypertensive properties after its oral administration to spontaneously hypertensive rats (SHR) [ 22 ]. In particular, AVFQHNCQE produced a NO-mediated antihypertensive effect and it was demonstrated that enhanced NO bioavailability through its antioxidant effect and by improving the endothelium functionality when administered to the hypertensive animals [ 23 ]. However, AVFQHNCQE vulnerability to GI enzymes and posterior absorption has not been studied yet.…”

Relationship between Nutrition and Alcohol Consumption with Blood Pressure: The ESTEBAN Survey

“…High-fructose corn syrup (HFCS) is the main source of added sweeteners in sweetened beverages. A high intake of HFCS causes an increase in BP and thus involves an increase in uric acid production which, in turn, results in a lowering of nitric oxide in the body [43,44]. Other hypotheses behind high SSB intake being implicated in hypertension involve decreased sodium excretion, activation of the sympathetic nervous system [45,46], or an increased sodium concentration in the body through increased gut absorption [47].…”

Dietary Bioactive Compounds and Human Health and Disease

“…In addition to these vegetable compounds, this issue includes novel findings regarding the implication of bioactive peptides, amino acids, and fatty acids in different metabolic outcomes. Mas-Capdevila et al raise interesting hypotheses about how the resistance of peptides to gastric digestion may modulate their antihypertensive effect [11], adding a novel approach to previous work about this topic [12,13]. At this point, factors such as bioavailability, synergistic effects between these compounds, or their interaction with other food components, are essential to deepening the knowledge of bioactive compounds on health [4].…”