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 activ ity of the inducible isoform of nitric oxide (NO) synthase in vitro. I n immunostimulated J774 macrophages, 2-iminopiperidine (EC(50) = 10 mu M) and butyramidine (EC(50) = 60 mu M) were more potent than N-G-meth yl-L-arginine (EC(50) = 70 mu M) 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 sou rce of the constitutive, endothelial NO synthase isoform) were less ef fective than N-G-nitro-L-arginine or N-G-methyl-L-arginine. The rank-o rder of the potencies of the amidines against the endothelial NO synth ase was, in general, similar to the rank-order of the presser effects of these agents in anesthetized rats. Thus, certain amidines are poten t inhibitors of NO synthase, and are more selective towards the induci ble NO synthase than the commonly used L-arginine based NO synthase in hibitors.