title: Attenuation of sodium nitroprusside responses after prolonged incubation of rat aorta with endotoxin.
abstract: We investigated the effects of prolonged treatment with Escherichia coli lipopolysaccharide (LPS) on the responses to sodium nitroprusside (SNP) in endothelium-denuded rat aortic strips. Incubation of the aortic strips with LPS for 24 h dramatically attenuated relaxation and guanosine 3',5'-cyclic monophosphate (cGMP) formation by SNP, which were significantly restored by the inhibition of nitric oxide (NO) production with N omega-nitro-L-arginine. In the aorta coincubated with LPS and protein synthesis inhibitor (dexamethasone or cycloheximide, which prevents induction of endotoxin-inducible NO synthase), no attenuation of the relaxation was observed and the cGMP formation was significantly restored. Relaxation response to 8-bromo-cGMP or papaverine was not attenuated, even after 24 h of incubation. These results suggest that the attenuation of SNP responses is mainly associated with a decrease in the activation of guanylate cyclase (GC) as a consequence of the prolonged exposure to muscle-derived NO. Moreover SNP in the presence of methylene blue evoked a small but apparent relaxation of 24-h-incubated aorta without significant elevation of cGMP, suggesting the involvement of cGMP-independent pathways in the remaining relaxation produced by SNP.
authors.affiliation: Department of Pediatrics and Pharmacology, Fukui Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsuchida
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
authors.forename: M
authors.initials: M
authors.lastname: Sudo
authors.forename: S
authors.initials: S
authors.lastname: Kigoshi
authors.forename: I
authors.initials: I
authors.lastname: Muramatsu
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli; D006162:Guanylate Cyclase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004731:Endotoxins; D009599:Nitroprusside; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D001120:Arginine; D010208:Papaverine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase; D006152:Cyclic GMP