Aminoguanidine selectively inhibits inducible nitric oxide synthase

Abstract

1 Endotoxin induces nitric oxide synthase in vascular tissue, including rat main pulmonary artery. Currently available agents that cause inhibition of nitric oxide synthase are relatively non-selective between the constitutive and inducible forms of the enzyme. 2 Aminoguanidine caused a dose-dependent increase in phenylephrine-induced tension in intact and endothelium-denuded pulmonary artery rings from endotoxin-treated rats, but had no effect on sham-treated controls. 3 Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was unaffected by indomethacin (10 μm), and by cimetidine and mepyramine (both 10 μm), excluding an effect of aminoguanidine mediated by arachidonic acid metabolites or histamine. 4 Contraction caused by aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was abolished by l-arginine (2 mm) and l-N^G-monomethyl arginine (300 μm), but unaffected by d-arginine and d-N^G-monomethyl arginine, suggesting that its action is mediated by the l-arginine/nitric oxide pathway. 5 Aminoguanidine had no effect on acetylcholine-induced relaxation of intact vessels from sham-treated rats. However, relaxation of artery rings from endotoxin-treated rats by l-arginine was competitively inhibited by aminoguanidine. 6 These results in isolated main pulmonary arteries of the rat confirm previous reports that aminoguanidine is a selective inhibitor of inducible nitric oxide synthase.