Yoshinori Kobayashi1, Kazuki Narita1, Kotaro Chiba1, Hiroaki Takemoto1, Masahiko Morita2, Koji Morishita2. 1. Laboratory of Pharmacognosy, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-0861, Japan. 2. Healthcare Products, Development Center, Kyowa Hakko Bio Co., Ltd, 2, Miyukigaoka, Tsukuba, Ibaraki, 305-0841, Japan.
Abstract
BACKGROUND: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae) and is a known component of the nitric oxide (NO) cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. OBJECTIVE: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model. MATERIALS AND METHODS: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C). A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice), and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. RESULTS: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. CONCLUSIONS: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.
BACKGROUND:L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae) and is a known component of the nitric oxide (NO) cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. OBJECTIVE: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivitymouse model. MATERIALS AND METHODS: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C). A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice), and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. RESULTS: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. CONCLUSIONS: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.
Authors: Toshio Hayashi; Packiasamy A R Juliet; Hisako Matsui-Hirai; Asaka Miyazaki; Akiko Fukatsu; Jun Funami; Akihisa Iguchi; Louis J Ignarro Journal: Proc Natl Acad Sci U S A Date: 2005-09-12 Impact factor: 11.205
Authors: Maarten P Koeners; Ernst E van Faassen; Sebastiaan Wesseling; Monique de Sain-van der Velden; Hein A Koomans; Branko Braam; Jaap A Joles Journal: Hypertension Date: 2007-10-15 Impact factor: 10.190