Nitric oxide and superoxide radical are involved in both initiation and development of adjuvant arthritis in rats.
Nitric oxide synthase(NOS) inhibitor,N omega-nitro-L-arginine methyl ester (L-NAME, 10-300 mg/kg) and L-NG-monomethyl-arginine (L-NMMA, 30-300 mg/kg) suppressed the swellings of adjuvant-injected paw of rats (25-54%) at day 2 and 8 when dosed intraperitoneally and orally for 4 days from day -1 to day 2 after adjuvant. L-NAME (30-300 mg/kg) also suppressed the edema of the non adjuvant-injected paws (15-42%) at day 28. Local injection of this inhibitor (2 and 10 mg/kg) was without effect. L-arginine (1 g/kg, i.p.), impaired the suppression by L-NAME. Bovine blood Cu, Zn-superoxide dismutase (SOD, 3 mg/kg, i.p.: 28% suppression) and L-NAME (30 mg/kg i.p.: 36% suppression) showed additive effect (52%) in adjuvant-injected paws at day 8 when co-injected. As the effect of 30 mg/kg L-NAME corresponded nearly to that of 10 mg/kg VoltarenR, this NOS inhibitor would be worth considering as an anti-inflammatory agent. Sodium nitroprusside (NO-donor) and methylene blue (guanylate cyclase inhibitor) had no effect. L-NAME was also suppressive when dosed after adjuvant inoculation and NO is involved in the development and maintenance of swelling.
Oyanagui
Y
Y
Drug Develop. Lab. Fujisawa Pharmaceut. Co., Osaka, Japan.
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000209:etiology*; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007274:Injections, Intraperitoneal; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019323:omega-N-Methylarginine
D013481:Superoxides; D004008:Diclofenac; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester