Polycyclic aromatic hydrocarbons-induced vasorelaxation through activation of nitric oxide synthase in endothelium of rat aorta.
In the present study, the effect of polycyclic aromatic hydrocarbons (PAHs) on isolated rat aorta was investigated. Acenaphthylene and naphthalene dose-dependently relaxed the phenylephrine-induced contraction of rat aorta with 50% vasorelaxation at 40.8+/-19.83 and 118.75+/-9.83 microM, respectively. The vasorelaxation effect was diminished in the denuded (endothelium removed) aorta suggesting that the relaxation effect of PAHs was endothelium dependent. By comparing PAHs with different ring structures, we have found that acenaphthylene has the highest potency to induce vasorelaxation. Pretreatment with the nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester, and the guanylate cyclase inhibitor, methylene blue, prevents the vasorelaxation induced by PAHs. These results indicate that the vasorelaxation effect of PAHs is mediated by activation of nitric oxide synthase of endothelium.
Kang
J J
JJ
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, ROC. jjkang@ccms.ntu.edu.tw
Cheng
Y W
YW
D000073:Acenaphthenes / Q000633:toxicity; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000073:Acenaphthenes; D009281:Naphthalenes; D011084:Polycyclic Aromatic Hydrocarbons; C042553:acenaphthylene; C031721:naphthalene; D019001:Nitric Oxide Synthase; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester