Dopamine as a novel antioxidative agent for rat vascular smooth muscle cells through dopamine D-1-Like receptors

Article

关键词: PHEOCHROMOCYTOMA;    PROLIFERATION;    EXPRESSION;    MIGRATION;    DISEASE;    GROWTH;   

DOI  :  10.1161/01.CIR.101.19.2302

来源: SCIE

【 摘 要 】

Background - To elucidate the roles of vascular D-1-like receptors in atherosclerosis, the effects of the specific D-1-like agonists on platelet-derived growth factor (PDGF)-BB-mediated oxidative stress in vascular smooth muscle cells (VSMCs) were studied. Methods and Results - Immunohistochemical studies demonstrated the coexistence of D-1A and D-1B dopamine receptors in VSMCs. Western blotting revealed a band of approximate to 70 kDa for D-1A and D-1B dopamine receptors. VSMCs stimulated by PDGF-BB exhibited increased oxidative stress directly measured by flow cytometry. These effects were prevented by dopamine, SKF 38393, or YM 435, and this prevention was reversed by Sch 23390. These effects were blocked by a specific protein kinase A (PKA) inhibitor, N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H 89). The PDGF-BB-mediated increase in oxidative stress of VSMCs was significantly suppressed by the indirect phospholipase D (PLD) inhibitor suramin or the specific protein kinase C (PKC) inhibitor calphostin C. Both antisense but neither sense nor scrambled oligonucleotides to D-1A and D-1B receptors inhibited dopamine-induced suppression of increase in oxidative stress of VSMCs induced by PDGF-BB. Conclusions - These findings suggest that vascular D-1-like receptors (D-1A and D-1B receptors) inhibit any increase in oxidative stress of VSMCs, possibly through activation of PKA and suppression of PLD and PKC.

【 授权许可】

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