The effects of hexasulfobutylated C60 (FC4S) and monomalonic acid C60 (MMA C60), the fullerene C60 derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C60 (10 μmol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C60 (10 μmol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC4S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC4S (10 μmol/l). In the denuded aortic rings, FC4S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC4S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 μmol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC4S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium.
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