Relaxation of rat thoracic aorta by N-nitroso compounds and nitroprusside and their modifications of nucleic acid bases through release of nitric oxide.
Nitroprusside and two newly synthesized direct-acting mutagens, N-nitroso-2-fluorenylactamide and N-nitroso-dinitroacetaminophen, were able to elicit the concentration-dependent relaxation of rat aorta. The vascular responses could be antagonized by hemoglobin that binds nitric oxide with high affinity and by methylene blue which inhibits soluble guanylate cyclase activity. We used four bases in DNA as the substrates to test the capacity to deaminate of the two compounds. Xanthine, hypoxanthine and uracil as well as some unusual bases such as 8-OH-adenine and 8-OH-guanine were found. These findings suggest that both the muscle relaxation and mutagenicity of these two compounds might be due to the release of nitric oxide in living cells.
Wang
J M
JM
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Republic of China.
Lin-Shiau
S Y
SY
Lin
J K
JK
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D000082:Acetaminophen / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D003641:Deamination; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006900:Hydroxylation; D008297:Male; D008751:Methylene Blue / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D009696:Nucleic Acids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D006454:Hemoglobins; D009603:Nitroso Compounds; D009696:Nucleic Acids; C057157:N-nitroso-N(2)-fluorenylacetamide; D008769:Methylnitronitrosoguanidine; C080275:N-nitroso-3,5-dinitroacetaminophen; D009599:Nitroprusside; D009569:Nitric Oxide; D000082:Acetaminophen; D015073:2-Acetylaminofluorene; D008751:Methylene Blue