ABSTRACT
1. Effects of a fullerene C60 derivative, monomalonic acid C60 (MMA C60), on endothelium-containing or denuded aorta of rabbit, trachea and ileum of guinea pig, and stomach (fundus), vas deferens and uterus of rat were studied pharmacologically. 2. MMA C60 (10(-5) M) significantly reduced the maximum response of the relaxation induced by acetylcholine in endothelium-containing thoracic aorta of rabbit, and the acetylcholine-induced relaxation was recovered in the presence of superoxide dismutase (SOD, 250 units/ml). 3. Nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused the relaxation of aorta without endothelium in a concentration-dependent manner, and the concentration-response curve was shifted to the right in the presence of MMA C60. This inhibitory effect of the derivative was also masked in the presence of superoxide dismutase (SOD). 4. Sodium nitroprusside-induced relaxation was not affected by either MMA C60 or SOD. In the other tissues, this C60 derivative had no effect on the responses induced by any agonist. 5. These observations indicate that MMA C60 inhibits the endothelium-dependent relaxation induced by acetylcholine but does not affect the agonist-induced contractile response of smooth muscle.
Subject(s)
Carbon/pharmacology , Fullerenes , Malonates/pharmacology , Muscle, Smooth, Vascular/drug effects , Nitric Oxide/antagonists & inhibitors , Acetylcholine/pharmacology , Adrenergic alpha-Agonists/pharmacology , Animals , Aorta, Thoracic/drug effects , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Guinea Pigs , Histamine/pharmacology , In Vitro Techniques , Male , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Nitric Oxide/pharmacology , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Rabbits , Rats , Trachea/drug effects , Vasodilator Agents/pharmacologyABSTRACT
Dimalonic acid C60 (10(-5) M), a new fullerene derivative, produced an augmentation of phenylephrine-induced tone and reduced both the acetylcholine-induced maximum relaxation and the amplitude of substance P (10(-8) M)-induced relaxation in endothelium-containing thoracic aorta of rabbit; the acetylcholine- and substance P-induced relaxation was restored in the presence of superoxide dismutase (250 U/ml). Dimalonic acid C60 (10(-5) M) did not influence the phenylephrine-induced contractile response in the absence of endothelium, but the acetylcholine-induced relaxation was eliminated by removal of the endothelium. Superoxide anion generation, using hypoxanthine (1 mM)/xanthine oxidase (16 mU/ml), reduced the acetylcholine-induced relaxation and produced an augmentation of phenylephrine-induced tone in endothelium-containing strips; these effects were negated by the addition of superoxide dismutase (250 U/ml). A nitric oxide-generating agent, S-nitroso-N-acetylpenicillamine, caused relaxation of aorta without endothelium in a concentration-dependent manner, and the concentration-response curve was shifted to the right in the presence of dimalonic acid C60. This inhibitory effect of dimalonic acid C60 was also masked in the presence of superoxide dismutase. Sodium nitroprusside-induced relaxation was not affected by either dimalonic acid C60 or superoxide dismutase. These observations suggest that dimalonic acid C60 inhibits endothelium (nitric oxide)-dependent agonist-induced relaxation through the production of superoxide.
