Dopamine as a Novel Antioxidative Agent for Rat Vascular Smooth Muscle Cells Through Dopamine D1-Like Receptors

Background—To elucidate the roles of vascular D1-like receptors in atherosclerosis, the effects of the specific D1-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 D1A and D1B dopamine receptors in VSMCs. Western blotting revealed a band of ≈70 kDa for D1A and D1B 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. Bot...