Food derived peptides with vasodilator effect. Structure-activity relationship
Biologically active peptide fragments are formed during proteolysis of food proteins, and have been shown to possess multiple physiological properties, including properties related to cardiovascular health such as blood pressure lowering effect. Most of food-derived peptides with antihypertensive activity have been also characterized as in vitro angiotensin converting enzyme (ACE) inhibitory agents, but, only a few studies have shown in vivo ACE-inhibitory activity of these peptides. This suggests that other mechanisms of action could be implicated in their antihypertensive effect. The aim of this study was to analyze, in resistance arteries, the vasodilator activity of several peptide sequences obtained from food protein hydrolysates and to establish whether there is a relationship between the aminoacids present in peptide sequences and the vasodilator effect. For this, third order branch of the mesenteric artery from 6 months old male Wistar Kyoto rats were used. The vasodilator response of arterial segments with or without endothelium to several peptides (0.1 mM) was analyzed in an isometric myograph. Moreover, the effect of NO synthase (L-NAME, 100 microM), and ciclooxygenase (indomethacin, 10 microM) inhibitors on the vasodilator response was tested. Peptides RADHPFL, RADHPF, RADHP, YRGGLEPINF, RDILNQ and VPP showed an endothelium-dependent vasorelaxation, whereas the vasodilator effect of FRADHPFL was only partially dependent of endothelium. The maximum relaxation (~75%), belongs to YRGGLEPINF peptide. In addition, the relaxation induced by the peptides RADHPFL, RADHPF, RADHP, RDILNQ and VPP is mainly mediated by NO, since the response was inhibited only by L-NAME, while both L-NAME and indomethacin inhibited the vasodilator response induced by FRADHPFL and YRGGLEPINF. It seems that the presence of arginine or tyrosine in the N-terminal extreme could be related with the vasodilator activity of these compounds. In conclusion, these results suggest that endothelium-dependent relaxation could be also a mechanism involved in the antihypertensive effect of food derived peptides.