Skip to main content
SpringerLink
Log in

The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Summary

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 concenrations 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Radomski MW, Palmer RMJ, Moncada S (1987) Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmac 92: 181–187

    Google Scholar 

  2. Radomski MW, Palmer RMJ, Moncada S (1987) Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet II: 1057–1058

    Google Scholar 

  3. Mellion BT, Ignarro LJ, Ohlstein EH, Pontecorvo EG, Hyman AL, Kadowitz PJ (1981) Evidence for the inhibitory role of guanosine 3′, 5′-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood 57: 946–955

    Google Scholar 

  4. Bath PMW, Hassall DG, Gladwin A-M, Palmer RMJ, Martin JF (1991) Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro. Arteriosclerosis Thrombosis 11: 254–260

    Google Scholar 

  5. Persson MG, Gustafsson LE, Wiklund NP, Hedqvist P, Moncada S (1990) Endogenous nitric oxide as a modulator of rabbit skeletal muscle microcirculation in vivo. Br J Pharmacol 100: 463–466

    Google Scholar 

  6. Kubes P, Suzuki M, Granger DN (1991) Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci 88: 4651–4655

    Google Scholar 

  7. Mehta J, Mehta P, Conti CR (1980) Platelet function studies in coronary heart disease. IX. Increased platelet prostaglandin generation and abnormal platelet sensitivity to prostacyclin and endoperoxide analog in angina pectoris. Am J Cardiol 46: 943–947

    Google Scholar 

  8. Gerzer R, Karrenbrock B, Siess W, Heim JM (1988) Direct comparison of the effects of nitroprusside, SIN-1, and various nitrates on platelet aggregation and soluble guanylate cyclase activity. Thromb Res 52: 11–21

    Google Scholar 

  9. Schafer AI, Alexander RW, Handin RI (1980) Inhibition of platelet function by organic nitrate vasodilators. Blood 55: 649–654

    Google Scholar 

  10. Bohme E, Grossman G, Spies C (1983) Effects of molsidomine and other NO-containing vasodilators on cyclic GMP formation. Europ Heart J 4 [Suppl C]: 19–24

    Google Scholar 

  11. Feelisch M (1991) The biochemical pathways of nitric oxide formation from nitrovasodilators: appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions. J Cardiovasc Pharmacol 17: S25-S33

    Google Scholar 

  12. Bath PMW, Booth RFG, Hassall DG (1989) Monocyte-lymphocyte discrimination in a new microtitre-based adhesion assay. J Immunol Methods 118: 59–65

    Google Scholar 

  13. Bath PMW, Mayston SA, Martin JF (1990) Endothelin and PDGF do not stimulate peripheral blood monocyte chemotaxis, adhesion to endothelium, and superoxide production. Exp Cell Res 187: 339–342

    Google Scholar 

  14. Bath PMW, Gladwin AM, Martin JF (1991) Hypercholesterolaemia is associated with increased monocyte function and expression of the CD11b adhesion receptor. Atherosclerosis 90: 175–181

    Google Scholar 

  15. Bruckdorfer KR, Buckley S, Hassall DG (1984) The effect of low-density lipoproteins on the synthesis of cyclic nucleotides induced by prostacyclin in isolated platelets. Biochem J 223: 189–196

    Google Scholar 

  16. Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 87: 206–210

    Google Scholar 

  17. Armitage P, Berry G (1987) Statistical methods in medical research. Blackwell, Oxford London

    Google Scholar 

  18. Gryglewski RJ, Korbut R, Kalecinska A, Zembowicz A (1989) Interaction between stimulators of adenylate and guanylate cyclases in human leukocytes, platelets and arteries. Int J Tiss Reac XI: 269–275

    Google Scholar 

  19. Fulle H-J, Endres S, Sinha B, Stoll D, Weber PC, Gerzer R (1991) Effects of SIN-1 on cytokine synthesis in human mononuclear cells. J Cardiovasc Pharmacol 17: S113-S116

    Google Scholar 

  20. Salvemini D, Masini E, Pistelli A, Mannaioni PF, Vane J (1991) Nitric oxide: a regulatory mediator of mast cell reactivity. J Cardiovasc Pharmacol 17: S258-S264

    Google Scholar 

  21. Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83: 1774–1777

    Google Scholar 

  22. Rapoport RM, Draznin MB, Murad F (1983) Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation. Nature 306: 174–176

    Google Scholar 

  23. Henderson AH, Morgan RO, Newby AC (1987) The inhibition by sodium nitroprusside of ADP-induced calcium influx and calcium mobilization in human platelets. J Physiol 387: 89P

  24. Feelisch M, Noack E, Schroder H (1988) Explanation of the discrepancy between the degree of organic decomposition, nitrite formation and guanylate cyclase stimulation. Europ Heart J 9 [Suppl A]: 57–62

    Google Scholar 

  25. Ahlner J, Andersson RGG, Torfgard K, Axelsson KL (1991) Organic nitrate esters. Clinical use and mechanisms of actions. Pharmacol Rev 43: 351–423

    Google Scholar 

  26. Benjamin N, Dutton JAE, Ritter JM (1991) Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate: evidence for generation of nitric oxide. Br J Pharmacol 102: 847–850

    Google Scholar 

  27. Nishikawa M, Kanamori M, Hidaka H (1982) Inhibition of platelet aggregation and stimulation of guanylate cyclase by an anti-anginal agent molsidomine and its metabolites. J Pharmacol Exp Therap 220: 183–190

    Google Scholar 

  28. Schini VB, Vanhoutte PM (1989) SIN-1 stimulates the production of cyclic GMP but not cyclic AMP in porcine aortic endothelial cells. J Cardiovasc Pharmacol 14: S91-S94

    Google Scholar 

  29. Waldman SA, Murad F (1989) Atrial natriuretic peptides: receptors and second messengers. BioEssays 10: 16–19

    Google Scholar 

  30. Strom TM, Weil J, Bidlingmaier F (1987) Platelet receptors for atrial natriuretic peptide in man. Life Sci 40: 769–773

    Google Scholar 

  31. DeCaterina R, Volpe M, Atlas SA, Weksler BB (1985) Effects of atrial natriuretic factor on human platelet function. Life Sci 37: 1395–1402

    Google Scholar 

  32. Bath PMW, MacGregor GA (1992) Sodium nitroprusside, a nitric oxide donor, inhibits monocyte chemotaxis and increases intracellular cGMP concentrations. Clin Sci 82: 32P

Download references

Author information

Authors and Affiliations

  1. Blood Pressure Unit, St. George's Hospital Medical School, London, UK

    P. M. W. Bath

Authors
  1. P. M. W. Bath
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bath, P.M.W. The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro. Eur J Clin Pharmacol 45, 53–58 (1993). https://doi.org/10.1007/BF00315350

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00315350

Key words

Search

Navigation