The milk-derived peptides Val-Pro-Pro and Ile-Pro-Pro attenuate arterial dysfunction in L-NAME-treated rats

Abstract

Both endothelial dysfunction and arterial stiffness are surrogate markers of atherosclerosis and thus cardiovascular (CV) events. The milk-derived peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) inhibit angiotensin-converting enzyme, dilate blood vessels ex vivo and stimulate nitric oxide (NO) production in cells. In this study, we investigated the effects of either VPP or IPP on arterial function and on target organ damage in vivo. Male Wistar rats were treated with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 g l(-1)), L-NAME+VPP (0.3 g l(-1)) or L-NAME+IPP (0.3 g l(-1)) in their drinking water for 8 weeks. Plasma nitrite and nitrate (NOx) levels were significantly increased in normal Wistar rats after supplementation with either VPP or IPP but not in rats that were chronically treated with L-NAME. Acetylcholine-induced vasorelaxation in the thoracic aorta ring was impaired by L-NAME, whereas vasorelaxation was significantly greater in mice treated with L-NAME+VPP for 1 or 4 weeks or L-NAME+IPP for 4 weeks than in mice treated with L-NAME alone. Four weeks of treatment with either VPP or IPP attenuated the increase in pulse wave velocity (PWV) that was induced by L-NAME. Cardiac and renal damage were observed after 8 weeks of treatment with L-NAME, and either VPP or IPP attenuated this damage. These results show that VPP or IPP attenuates arterial dysfunction and suggest that milk-derived peptides might prevent CV damage.

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

“…In fact, the inhibition of this enzyme is the main mechanism implied in the anti-hypertensive effect of dietary peptides [9,10,11]. In addition, endothelial function, which maintains normal vascular tone and blood fluidity to maintain normotensive BP values, has been demonstrated to be the target for some anti-hypertensive peptides [12,13,14]. In HTN, endothelial function is impaired, which presents a decreased presence of vasodilator factors, such as nitric oxide (NO) or prostacyclin (PGI 2 ), and/or increased presence of endothelium-derived contracting factors, such as endothelin 1 (ET-1) [15].…”

The Potential of Food Protein-Derived Bioactive Peptides against Chronic Intestinal Inflammation

“…Numbers of BAPs derived from various food proteins (milk, plant, egg, soybean, meat, wheat, rice, potato, corn silk, fish, etc.) have been found to be well suited to treat inflammation or IBD symptoms in vivo ( Table 2 ), such as Ala-Gln (AQ) [ 9 , 52 – 54 ], DIKTNKPVIF [ 45 ], EWP [ 55 ], GLTSK [ 56 ], glycomacropeptide [ 57 – 60 ], lunasin [ 15 ], IRW [ 11 , 61 – 63 ], IQW [ 62 – 64 ], KGHYAERVG [ 65 ], KPV [ 66 ], PTGADY [ 67 ], QCQCAVEGGL [ 68 ], QEPVL, QEPV [ 6 ], RILSILRHQNLLKELQDLAL [ 69 ], SSEDIKE [ 70 ], TMKLLLVTL [ 43 ], VPP [ 31 , 46 , 71 , 72 ], IPP [ 71 , 72 ], VPY [ 33 ], WH [ 41 ], casein hydrolysates [ 73 ], soybean dipeptides and tripeptides [ 74 ], peptide P-317 [ 75 ], pyroGlu-Leu [ 76 ], β -Casofensin [ 77 ], γ -EC, and γ -EV [ 47 ]. These studies suggest that oral administration of food-derived BAPs have anti-inflammatory effects, and they can be the therapeutic agents for inflammatory-related diseases, including IBD [ 78 ].…”

“…Proinflammatory IL-6 and IL-1 β were reduced, and atherosclerosis was attenuated by oral administration of VPP and IPP [ 71 ]. Arterial dysfunction was attenuated by drinking water with VPP and IPP through increasing vasorelaxation and nitrite and nitrate and reducing pulse wave velocity and cardiac and renal damage [ 72 ]. It was reported that VPP attenuated inflammation via the MAPK-JNK pathway by reducing monocytes, macrophages, CD18, IL-6, and MCP-1 in adipose inflammatory mice [ 46 ].…”

Perspectives on the Potential Benefits of Antihypertensive Peptides towards Metabolic Syndrome

“…ACE inhibitory peptides with potential antihypertensive properties have been identified from both animal and plant sources [122,123]. VPP and IPP are the well-known casein-derived tripeptides with antihypertensive, vasculo-protective, antioxidant, and anti-inflammatory properties as shown in vivo [124][125][126][127]. The reported effect of these peptides on reducing blood pressure in clinical trials is controversial [128][129][130][131] and needs further investigation.…”