Stimulatory and inhibitory action of nitric oxide donor agents vs. nitrovasodilators on reactive oxygen production by isolated polymorphonuclear leukocytes.
Nitrovasodilators, particularly the nitric oxide donor agents, are known to inhibit leukocyte functions such as chemotaxis, adherence, migration and proteolytic enzyme release. In this study, we investigated the modulatory role of nitric oxide donor agents on reactive oxygen production by canine polymorphonuclear leukocytes using luminol-enhanced chemiluminescence (LDCL). LDCL was measured before and after activation using 1 mg/ml of opsonized zymosan in the absence or presence of various agents. Unlike the nitrovasodilators, nitroglycerin and nicorandil, the nitric oxide donor agents, 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside, both produced enhanced stimulation of LDCL following zymosan at low concentrations of the agonist and inhibition at high concentrations of the agonist. SIN-1 and sodium nitroprusside (but not nitroglycerin or nicorandil) also produced LDCL before activation of cells with zymosan. This increase was blocked by superoxide dismutase or catalase but not by the hydroxyl radical scavenger, mannitol. SIN-1c, the inactive product of SIN-1 produced no LDCL. Furthermore, incubation of 10 microM SIN-1 or nitroprusside with luminol in the absence of cells produced no chemiluminescence at these drug concentrations. The stimulation of LDCL in the prezymosan phase was partially inhibited by methylene blue and L-nitroarginine methyl ester. In zymosan-stimulated cells, the enhanced LDCL induced by SIN-1 was prevented with superoxide dismutase, catalase (but not mannitol) and reversed with L-nitroarginine methyl ester. Thus, nitric oxide donor agents may either stimulate or inhibit oxygen radical production by isolated neutrophils depending on the drug concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Pieper
G M
GM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Clarke
G A
GA
Gross
G J
GJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D016166:Free Radical Scavengers; D008163:Luminescent Measurements; D008165:Luminol; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D008165:Luminol; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D019331:NG-Nitroarginine Methyl Ester