Inhibitory effects of a fullerene derivative, dimalonic acid C60, on nitric oxide-induced relaxation of rabbit aorta.
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.
Satoh
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan. satoh@phar.toho-u.ac.jp
Matsuo
K
K
Kiriya
H
H
Mashino
T
T
Nagano
T
T
Hirobe
M
M
Takayanagi
I
I
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010656:Phenylephrine; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D008314:Malonates; D014662:Vasoconstrictor Agents; C107223:dimalonic acid C(60); D010656:Phenylephrine; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000109:Acetylcholine