The milk-derived peptides Val-Pro-Pro and Ile-Pro-Pro attenuate arterial dysfunction in L-NAME-treated rats.
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.
Microbiology & Fermentation Laboratory, Calpis Co., Ltd., Kanagawa, Japan.
Atsuko
A
Nonaka
Microbiology & Fermentation Laboratory, Calpis Co., Ltd., Kanagawa, Japan.
Teppei
T
Nakamura
Microbiology & Fermentation Laboratory, Calpis Co., Ltd., Kanagawa, Japan.
Tatsuhiko
T
Hirota
Microbiology & Fermentation Laboratory, Calpis Co., Ltd., Kanagawa, Japan.
Akiko
A
Matsushita
Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan.
Masanori
M
Asakura
Microbiology & Fermentation Laboratory, Calpis Co., Ltd., Kanagawa, Japan.
Kohji
K
Ohki
Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita, Japan.
Masafumi
M
Kitakaze
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D008297:Male; D008892:Milk / Q000737:chemistry*; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000494:pharmacology*; D063177:Pulse Wave Analysis; D051381:Rats; D017208:Rats, Wistar; D014652:Vascular Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D014665:Vasodilator Agents; C489032:isoleucyl-prolyl-proline; C489031:valyl-prolyl-proline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester