The effects of the nitric oxide donors molsidomine and SIN-I on human polymorphonuclear leucocyte function in vitro and ex vivo.
The nitrovasodilator and nitric oxide donor molsidomine and its metabolite SIN-I dilate vascular smooth muscle and inhibit platelet activation by increasing intracellular concentrations of cyclic GMP. We have therefore studied the effects of molsidomine and SIN-I on isolated human polymorphonuclear leucocytes (PMN) in vitro and ex vivo. In vitro molsidomine dose-dependently reduced beta-glucuronidase release and the generation of superoxide anions from non-activated and from FMLP- or PAF-stimulated human PMNs. SIN-I was equally effective in reducing beta-glucuronidase release and totally inhibited oxygen radical generation at a concentration of 580 mumol.l-1. In a double-blind, placebo-controlled, randomized trial we also studied beta-glucuronidase release and the generation of superoxide anions from isolated PMNs. Blood was drawn from 12 healthy volunteers before and 3 h after oral molsidomine (16 mg) or placebo. There was no statistically significant difference in beta-glucuronidase release and superoxide anion formation when the PMNs were isolated before or after molsidomine or placebo. This was the case for non-activated, as well as FMLP- or PAF-stimulated PMNs. Thus, the nitric oxide donors molsidomine and its metabolite SIN-I caused a dose-dependent inhibition of PMN functions in vitro, but no significant inhibition when the PMNs were isolated after oral molsidomine.
Darius
H
H
II. Medizinische Klinik, Klinisch-Pharmakologisches Labor, Johannes Gutenberg Universität, Mainz, FRG.
Grodzinska
L
L
Meyer
J
J
D000328:Adult; D004311:Double-Blind Method; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C002385:linsidomine; D008981:Molsidomine; D005966:Glucuronidase