Amidines are potent inhibitors of nitric oxide synthases: preferential inhibition of the inducible isoform

We evaluated the ability of simple alkyl amidines to inhibit the activity of the inducible isoform of nitric oxide (NO) synthase in vitro. In immunostimulated J774 macrophages, 2-iminopiperidine (EC₅₀ = 10 μM) and butyramidine (EC₅₀ = 60 μM) were more potent than N^G-methyl-L-arginine (EC₅₀ = 70 μM) in inhibiting nitrite formation. The five amidines tested for their ability to inhibit the conversion of L-arginine to L-citrulline by bovine endothelial cell homogenates (a source of the constitutive, endothelial NO synthase isoform) were less effective than N^G-nitro-L-arginine or N^G-methyl-L-arginine. The rank-order of the potencies of the amidines against the en endothelial NO synthase was, in general, similar to the rank-order of the pressor effects of these agents in anesthetized rats. Thus, certain amidines are potent inhibitors of NO synthase, and are more selective towards the inducible NO synthase than the commonly used L-arginine based NO synthase inhibitors.