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European Journal of Clinical Pharmacology

, Volume 43, Issue 6, pp 629–633 | Cite as

The effects of the nitric oxide donors molsidomine and SIN-1 on human polymorphonuclear leucocyte functionin vitro andex vivo

  • H. Darius
  • L. Grodzinska
  • J. Meyer
Originals

Summary

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 andex vivo.

In vitro molsidomine dose-dependently reducedβ-glucuronidase release and the generation of superoxide anions from non-activated and from FMLP- or PAF-stimulated human PMNs. SIN-1 was equally effective in reducing (β-glucuronidase release and totally inhibited oxygen radical generation at a concentration of 580 μmol · l−1.

In a double-blind, placebo-controlled, randomized trial we also studiedβ-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 inβ-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 functionsin vitro, but no significant inhibition when the PMNs were isolated after oral molsidomine.

Key words

Molsidomine, SIN-I, Neutrophil leucocytes Aglucuronidase, superoxide anions 

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • H. Darius
    • 1
  • L. Grodzinska
    • 2
  • J. Meyer
    • 1
  1. 1.II. Medizinische KlinikJohannes Gutenberg UniversitätMainz 1Germany
  2. 2.Department of Pharmacology, Division of Clinical PharmacologyCopernicus Medical AcademyCracowPoland

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