L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive oxygen species in rat aorta

Abstract

Objectives: 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 Nω̄-Nitro-L-arginine (L-NNA), Sodium nitroprusside (SNP) in endothelium-intact and endothelium-denuded aortic rings. Results: L-DOPA potentiated α-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.