Aminoguanidine inhibits both constitutive and inducible nitric oxide synthase isoforms in rat intestinal microvasculature in vivo

European Journal of Pharmacology
F LászlóB J Whittle

Abstract

The effects of aminoguanine on the intestinal vascular permeability following endotoxin administration in vivo has been compared to those of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in the rat. Concurrent administration of aminoguanidine. (12.5-50 mg/kg, s.c.) with endotoxin (E. coli lipopolysaccharide, 3 mg/kg, i.v.), dose dependently increased vascular leakage of radiolabelled albumin in the ileum and colon after 1 h, an effect reversed by the pretreatment with L-arginine (300 mg/kg, s.c.). Aminoguanidine (50 mg/kg, s.c.) also elevated arterial blood pressure over the 1 h investigation period. Similar acute potentiation of endotoxin-provoked vascular injury was observed 1 h following L-NMMA (50 mg/kg s.c.) which also increased blood pressure, indicating the inhibition of constitutive NO synthase. By contrast, administration of aminoguanidine (12.5-50 mg/kg, s.c.) 3 h after endotoxin, at the time of the expression of the inducible NO synthase, reduced the subsequent endotoxin-induced vascular leakage, as did L-NMMA (50 mg/kg). In homogenates of rat ileal or colonic tissue, aminoguanidine inhibited both the constitutive and inducible NO synthase activity showing only 2-fold selectivity for the ...Continue Reading

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