title: L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive oxygen species in rat aorta.
abstract: OBJECTIVE
  To clarify the underlying mechanisms of L-DOPA induced vasoconstriction in rat aorta.
  
  
  METHODS
  The effect of L-DOPA on phenylephrine-induced contractile force of blood vessels was examined in vitro using rat aortic ring preparations by isometric tension experiment. Involvement of nitric oxide (NO) in the effect of L-DOPA on vascular smooth muscle was studied by using N(omega)-Nitro-L-arginine (L-NNA), Sodium nitroprusside (SNP) in endothelium-intact and endothelium-denuded aortic rings.
  
  
  RESULTS
  L-DOPA potentiated alpha-adrenergic receptor- and depolarization-induced vascular contraction and inhibited acetylcholine-induced vasorelaxation. This effect was diminished by pretreatment of the aortic rings with L-NNA, an inhibitor of NO synthesis, or by removing the endothelium from the ring preparations. In endothelium-denuded rings, L-DOPA inhibited exogenous NO-dependent but not cGMP-mediated vasorelaxation. Increases in cGMP levels in response to an NO donor were attenuated by L-DOPA in cultured rat aortic smooth muscle cells. L-DOPA could not contract rings (without endothelium) pretreated with 3-(5'-hydroxymethyl- 2'-furyl)-1-benzyl indazole (YC-1), an activator of guanylyl cyclase, but SOD (150 U/ml) pretreatment of rings with endothelium inhibited contraction by L-DOPA.
  
  
  CONCLUSIONS
  These results suggest that L-DOPA inhibits nitric-dependent vasorelaxation on vascular smooth muscle cells via production of reactive oxygen species.
authors.affiliation: Department of Anesthesiology, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.
authors.lastname: Yinhua
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Sonoko
authors.initials: S
authors.lastname: Yasui
authors.forename: Hiroko
authors.initials: H
authors.lastname: Segawa
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Shuzo
authors.initials: S
authors.lastname: Oshita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000502:physiology; D066298:In Vitro Techniques; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D010656:Phenylephrine; D009569:Nitric Oxide; D007980:Levodopa; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP