This study was undertaken to determine whether silver nanoparticles (Ag-45 nm NPs) induce selective and specific biological effects, such as induction of proliferation and nitric oxide (NO) production, and cytotoxicity in coronary endothelial cells (CECs), and regulation of vascular tone in isolated rat aortic rings. Physical characterization of Ag-45 nm NPs by transmission electron microscopy (TEM) demonstrated that nanoparticles ranging in size from 10 to 90 nm had biological effects on CECs. Increasing concentrations of Ag-45 nm NPs exerted a dual effect on cell proliferation whereby proliferation was inhibited at low concentrations of NPs and stimulated at high concentrations. The effects of high, but not low, concentrations of Ag-45 nm NPs were dependent on NO because the effects were partially blocked by NG-nitro-l-arginine methyl ester (L-NAME). We have also shown that high, but not low, concentrations of Ag-45 nm NPs induce NO-dependent proliferation through activation of endothelial nitric oxide synthase (eNOS) by phosphorylation of Serine 1177. Moreover, the antiproliferative and proliferative effects of Ag-45 nm NPs were concentration-dependent and inversely correlated with cellular toxicity. In isolated rat aortic rings, a low concentration of NPs induced vasoconstriction and a high concentration stimulated vasodilation. The physiologic effects induced by a low concentration of Ag-45 nm NPs inhibited acetylcholine- (ACh-) induced NO-mediated relaxation. Vasodilation induced by a high concentration of NPs was partially abolished by L-NAME pretreatment. When the endothelium was removed from the rings, all physiologic responses were blocked. These results clearly demonstrate that the NPs have selective and specific effects on the vascular endothelium in a concentration-dependent manner and suggest that opposite effects could be associated with NPs of different sizes.
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