The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro.
The effects of sodium nitroprusside (SNP) and 3-morpholino sydnonimine (SIN-1), isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN), and molsidomine (the inactive precursur of SIN-1) on monocyte chemotaxis and cyclic GMP (cGMP) concentration were studied. SNP and SIN-1 inhibited monocyte N-formyl-methionyl-leucyl-phenylalanine-stimulated migration and increased cGMP concentrations in a dose-dependent (> 10(-5) mol.l-1) and time-dependent manner. Furthermore, 8-bromo cGMP inhibited monocyte chemotaxis in a dose-dependent fashion. In contrast, ISDN, GTN and molsidomine did not alter monocyte migration or cGMP concentration. These results support earlier observations that nitric oxide inhibits monocyte function in vitro via a cGMP-mediated mechanism. The differential effects of the spontaneous and thiol-dependent NO-donating nitrovasodilators on monocyte function suggests that monocytes, like platelets, are not able to directly metabolise ISDN and GTN. If similar observations can be made in vivo, it is possible that certain nitrovasodilators might be used therapeutically to inhibit monocyte function, for example during atherogenesis.
Bath
P M
PM
Blood Pressure Unit, St. George's Hospital Medical School, London, UK.
D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006152:Cyclic GMP / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; C002385:linsidomine; D008981:Molsidomine; D005996:Nitroglycerin; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate