title: Milk casein-derived tripeptides, VPP and IPP induced NO production in cultured endothelial cells and endothelium-dependent relaxation of isolated aortic rings.
abstract: Milk casein-derived tripeptides, valyl prolyl proline (VPP), and isoleucyl prolyl proline (IPP) inhibit angiotensin-converting enzyme (ACE) and both fermented milk and proteolytic hydrolysates of milk casein containing these peptides exert blood pressure-lowering effects in animals and humans. On the top of these results, we have recently reported that the hydrolysate of milk casein containing both VPP and IPP improved the vascular endothelial function of subjects with stage I hypertension, enforcing us to elucidate the mechanism of the improvement of endothelial dysfunction by these peptides. For this purpose, we examined the effect of VPP and IPP on induction of nitric oxide (NO) production using cultured vascular endothelial cells and isolated arterial vessels. When both VPP and IPP were added to the medium of cultured endothelial cells at final concentrations of more than 100 nmol/l, the NO(x) (NO(2) and NO(3)) concentration in the medium was significantly higher than that of the control. Moreover, both VPP and IPP induced endothelium-dependent relaxation of isolated aortic rings, and these effects were inhibited by NO synthase inhibitors, K channel inhibitors, and bradykinin B2 receptor antagonists. These lines of results suggested that both VPP and IPP induced production of vasodilative substances including NO.
authors.affiliation: Microbiology and Fermentation Laboratory, Calpis Co., Ltd., 5-11-10 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-0206, Japan. tatsuhiko.hirota@calpis.co.jp
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Hirota
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nonaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsushita
authors.forename: Naoto
authors.initials: N
authors.lastname: Uchida
authors.forename: Kohji
authors.initials: K
authors.lastname: Ohki
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D065094:Bradykinin B2 Receptor Antagonists; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D026902:Potassium Channel Blockers; D043782:Receptor, Bradykinin B2; D014665:Vasodilator Agents; C489032:isoleucyl-prolyl-proline; C489031:valyl-prolyl-proline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A