title: Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric dimethylarginine pathway in rat type II diabetic nephropathy.
abstract: An impaired generation of nitric oxide has been associated with diabetic renal disease. In order to elucidate the underlying molecular mechanisms into how nitric oxide synthesis is impaired in diabetic renal disease, we examined changes in activities and expressions of some renal enzymes involved in nitric oxide production during the development of diabetic nephropathy in type II diabetic Otsuka Long-Evans Tokushima Fatty rats. Ten-week old Otsuka Long-Evans Tokushima Fatty (n = 40) and control Long-Evans Tokushima Otsuka rats (n = 20) were given drinking water containing 20% sucrose to accelerate the development of diabetic nephropathy. Otsuka Long-Evans Tokushima Fatty rats developed diabetic nephropathy in an age-dependent manner. Renal nitric oxide synthase activities in Otsuka Long-Evans Tokushima Fatty rats gradually declined with the progression of diabetic mellitus and were significantly lower than those of age-matched Long-Evans Tokushima Otsuka rats after 22 weeks of age. The lower activities of renal nitric oxide synthase in Otsuka Long-Evans Tokushima Fatty rats were correlated with relatively higher levels of renal free asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and were also correlated with decreased activities of dimethylargininedimethylaminohydrolase which metabolizes asymmetric dimethylarginine to citrulline. These results imply that dimethylargininedimethylaminohydrolase dysregulation may play an important role in the development of diabetic nephropathy by increasing asymmetric dimethylarginine levels, which leads to inhibition of renal nitric oxide synthesis.
authors.affiliation: Laboratory of Biochemistry and Global Center of Excellence Program, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Ying-Ling
authors.initials: YL
authors.lastname: Lai
authors.forename: Sae
authors.initials: S
authors.lastname: Aoyama
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ohata
authors.forename: Nami
authors.initials: N
authors.lastname: Otsuka
authors.forename: Hidemi
authors.initials: H
authors.lastname: Shiokawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomono
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Miyoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohshima