L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive oxygen species in rat aorta.
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.
Yinhua
Department of Anesthesiology, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.
Harada
Nagakatsu
N
Mawatari
Kazuaki
K
Yasui
Sonoko
S
Segawa
Hiroko
H
Takahashi
Akira
A
Oshita
Shuzo
S
Nakaya
Yutaka
Y
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
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