SELECTIVE-INHIBITION OF THE 12-LIPOXYGENASE PATHWAY OF ARACHIDONIC-ACID METABOLISM BY L-ARGININE OR SODIUM-NITROPRUSSIDE IN INTACT HUMAN PLATELETS

L-arginine (1-100 mu M) or sodium nitroprusside (1-100 mu M) caused a concentration dependent decrease in the metabolism of exogenously added arachidonic acid via the 12-lipoxygenase pathway in intact human platelets, as determined by the use of an HPLC assay. N-G-monomethyl-L-arginine, but not the D-isomer of this compound, diminished the inhibitory effect of L-arginine. The D isomer of arginine had no effect. The cyclooxygenase pathway was much less susceptible to these effects. This study indicated that nitric oxide formed in intact human platelets selectively inhibited 12-lipoxygenase over that of cyclooxygenase and suggests that such inhibition may be an important regulatory mechanism. (C) 1994 Academic Press, Inc.