title: Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice.
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.
  
  
  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.affiliation: Laboratory of Pharmacognosy, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-0861, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Pharmacognosy, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-0861, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Narita
authors.affiliation: Laboratory of Pharmacognosy, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-0861, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Laboratory of Pharmacognosy, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-0861, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takemoto
authors.affiliation: Healthcare Products, Development Center, Kyowa Hakko Bio Co., Ltd, 2, Miyukigaoka, Tsukuba, Ibaraki, 305-0841, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morita
authors.affiliation: Healthcare Products, Development Center, Kyowa Hakko Bio Co., Ltd, 2, Miyukigaoka, Tsukuba, Ibaraki, 305-0841, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Morishita
keywords: Citrullus lanatus; Cucurbitaceae; L-citrulline; cold hypersensitivity; nitric oxide