INHIBITION OF ARGINASE BY N-G-HYDROXY-L-ARGININE IN ALVEOLAR MACROPHAGES - IMPLICATIONS FOR THE UTILIZATION OF L-ARGININE FOR NITRIC-OXIDE SYNTHESIS

The hypothesis was investigated that the nitric oxide (NO) synthase intermediate, N-G-hydroxy-L-arginine (HOArg), is an arginase inhibitor in rabbit or rat alveolar macrophages, Exogenously applied HOArg strongly inhibited the arginase activity present in these cells (IC(50)greater than or equal to 15 mu M), and attenuated L-[H-3]arginine transport (IC50 greater than or equal to 500 mu M) in rabbit alveolar macrophages. Moreover, up to 37 mu M HOArg were detected in the conditioned medium, but not in the lysate, of rat alveolar macrophages exposed to bacterial lipopolysaccharide for 18 h, HOArg may thus be a potent endogenous arginase inhibitor in these cells which increases the availability of L-arginine for NO biosynthesis.