ANTAGONISM BY PARAQUAT OF THE RELAXING EFFECTS OF ACETYLCHOLINE AND A23187 IN RAT THORACIC AORTA

Paraquat, a widely used herbicide, has been reported to be capable of producing superoxide. In the present paper, therefore, the possibility of paraquat inhibiting endothelium-dependent relaxation, mediated by the production of nitric oxide, was tested. The relaxing effects of ac etylcholine and A23187, but not that of sodium nitroprusside, in the r at thoracic aorta were found to be inhibited by paraquat in a concentr ation-dependent manner. In contrast, paraquat was totally inactive wit h regard to the aortic contractions induced by either norepinephrine o r prostaglandin F-2 alpha. The inhibitory action of paraquat could be antagonized by superoxide dismutase but not by catalase and indomethac in. All of these findings indicate that superoxide anions produced by paraquat in the endothelium contribute to a decrease in the relaxation response to acetylcholine and A23187 by interfering with endothelium- derived nitric oxide.