title: Creatinine metabolite, HMH (5-hydroxy-1-methylhydantoin; NZ-419), modulates bradykinin-induced changes in vascular smooth muscle cells.
abstract: A creatinine metabolite, 5-hydroxy-1-methylhydantoin (HMH: NZ-419), a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. In the current study, we demonstrate that HMH modulates the effects of glucose and bradykinin (BK) in vascular smooth muscle cell (VSMC). HMH a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling. HMH inhibited the BK-induced increase in MAPK phosphorylation and attenuated the increase in connective tissue growth factor (CTGF) protein levels in VSMC. These findings suggest that HMH may confer vascular protection against high glucose concentrations and BK-stimulation to ameliorate vascular injury and remodeling through its anti-oxidant properties.
authors.affiliation: Nippon Zoki Pharmaceutical Co., Ltd. , Chuo-ku, Osaka , Japan .
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Ienaga
authors.forename: Mimi
authors.initials: M
authors.lastname: Sohn
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Naiki
authors.forename: Ayad A
authors.initials: AA
authors.lastname: Jaffa
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D006827:Hydantoins / Q000008:administration & dosage*; D017665:Hydroxyl Radical; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006827:Hydantoins; D017665:Hydroxyl Radical; C058007:5-hydroxy-1-methylhydantoin; D005947:Glucose; D001920:Bradykinin
keywords: BK-B2 receptor; CTGF; HMH (NZ-419); MAPK; intrinsic anti-oxidant