N-G-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE FORMATION, REVERSES IL-2-MEDIATED HYPOTENSION IN DOGS

N-G-methyl-L-arginine, an inhibitor of nitric oxide formation, reverse s IL-2-mediated hypotension in dogs. J. Appl. Physiol. 76(3): 1130-113 7, 1994. - The effects of N-G-methyl-L-arginine (L-NMA), an inhibitor of nitric oxide formation, were studied in dogs treated with interleuk in-2 (IL-2). The administration of IL-2 to dogs resulted in hypotensio n within 3 days of treatment. The development of hypotension correlate d with accumulation in the serum of nitrate, which is a stable breakdo wn product of nitric oxide. Administration of L-NMA decreased serum ni trate levels and increased the mean arterial pressure. The antihypoten sive effect was dose dependent with a maximum effect observed at a dos e of 20 mg/kg. Administration of a continuous infusion of L-NMA (5 mg. kg(-1).h(-1)) maintained the mean arterial pressure for 48 h with conc urrent administration of IL-2. Evaluation of IL-2-induced lymphokine-a ctivated killer cell proliferation and tumoricidal activity toward a c anine glioblastoma target cell line was unaffected by L-NMA. These stu dies imply that L-NMA may effectively ameliorate the dose-limiting hyp otension associated with administration of IL-2 without adversely affe cting the antitumor effects.