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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1992 Mar;33(3):289–292. doi: 10.1111/j.1365-2125.1992.tb04037.x

Prostaglandin I2 and the nitric oxide donor molsidomine have synergistic effects on thromboresistance in man.

H Sinzinger 1, F Rauscha 1, J O'Grady 1, P Fitscha 1
PMCID: PMC1381277  PMID: 1576049

Abstract

1. In vitro synergistic effects of nitric oxide and prostaglandin I2 (PGI2) have been shown. Consequently we examined any potentiating effect of the nitric oxide donor molsidomine on the reduction in thrombogenicity produced by PGI2 in patients with peripheral vascular disease. 2. Thirty-six patients all with peripheral and also coronary artery disease were randomly allocated to receive PGI2 5 ng kg-1 min-1 for 6 h daily, 5 days a week for 5 weeks, alone (12 patients), with molsidomine 12 mg daily (12 patients) or molsidomine 12 mg daily alone (12 patients). 3. The effect of each treatment regimen was measured in terms of femoral artery platelet uptake and platelet survival after autologous 111Indium-oxine labelling. Molsidomine alone had no effect on platelet uptake or survival but in combination with PGI2 it significantly potentiated the decreased platelet uptake and prolonged platelet survival observed with PGI2 alone.

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Selected References

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  1. Berenger-Bahuet F. P., Rolland P. H. The long-term exposure of endothelial cells to molsidomine increases their antithrombogenicity by inducing the production of nitric oxide-related chemical substances. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S98–105. [PubMed] [Google Scholar]
  2. Bohn H., Schönafinger K. Oxygen and oxidation promote the release of nitric oxide from sydnonimines. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S6–12. [PubMed] [Google Scholar]
  3. Böhme E., Grossman G., Spies C. Effects of molsidomine and other NO-containing vasodilators on cyclic GMP formation. Eur Heart J. 1983 May;4 (Suppl 100):19–24. doi: 10.1093/eurheartj/4.suppl_c.19. [DOI] [PubMed] [Google Scholar]
  4. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  5. Gerzer R., Karrenbrock B., Siess W., Heim J. M. Direct comparison of the effects of nitroprusside, SIN 1, and various nitrates on platelet aggregation and soluble guanylate cyclase activity. Thromb Res. 1988 Oct 1;52(1):11–21. doi: 10.1016/0049-3848(88)90036-9. [DOI] [PubMed] [Google Scholar]
  6. Gorman R. R., Bunting S., Miller O. V. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. doi: 10.1016/0090-6980(77)90018-1. [DOI] [PubMed] [Google Scholar]
  7. Kamata K., Miyata N., Kasuya Y. Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats. Br J Pharmacol. 1989 Jun;97(2):614–618. doi: 10.1111/j.1476-5381.1989.tb11993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Katzenschlager R., Weiss K., Rogatti W., Stelzeneder M., Sinzinger H. Interaction between prostaglandin E1 and nitric oxide (NO). Thromb Res. 1991 May 15;62(4):299–304. doi: 10.1016/0049-3848(91)90150-u. [DOI] [PubMed] [Google Scholar]
  9. Keren G., Katz S., Strom J., Sonnenblick E. H., LeJemtel T. H. Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure. Circulation. 1989 Aug;80(2):306–313. doi: 10.1161/01.cir.80.2.306. [DOI] [PubMed] [Google Scholar]
  10. Ludmer P. L., Selwyn A. P., Shook T. L., Wayne R. R., Mudge G. H., Alexander R. W., Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986 Oct 23;315(17):1046–1051. doi: 10.1056/NEJM198610233151702. [DOI] [PubMed] [Google Scholar]
  11. Moncada S., Palmer R. M., Higgs E. A. The discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension. 1988 Oct;12(4):365–372. doi: 10.1161/01.hyp.12.4.365. [DOI] [PubMed] [Google Scholar]
  12. Moncada S., Radomski M. W., Palmer R. M. Endothelium-derived relaxing factor. Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem Pharmacol. 1988 Jul 1;37(13):2495–2501. doi: 10.1016/0006-2952(88)90236-5. [DOI] [PubMed] [Google Scholar]
  13. Ney P., Schröder H., Schrör K. Nitrovasodilator-induced inhibition of LTB4 release from human PMN may be mediated by cyclic GMP. Eicosanoids. 1990;3(4):243–245. [PubMed] [Google Scholar]
  14. Patrono C., Ciabattoni G., Pinca E., Pugliese F., Castrucci G., De Salvo A., Satta M. A., Peskar B. A. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res. 1980 Feb 1;17(3-4):317–327. doi: 10.1016/0049-3848(80)90066-3. [DOI] [PubMed] [Google Scholar]
  15. Radomski M. W., Palmer R. M., Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987 Nov 7;2(8567):1057–1058. doi: 10.1016/s0140-6736(87)91481-4. [DOI] [PubMed] [Google Scholar]
  16. Radomski M. W., Palmer R. M., Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol. 1987 Nov;92(3):639–646. doi: 10.1111/j.1476-5381.1987.tb11367.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shimokawa H., Vanhoutte P. M. Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis. Circ Res. 1989 May;64(5):900–914. doi: 10.1161/01.res.64.5.900. [DOI] [PubMed] [Google Scholar]
  18. Sinzinger H., Fitscha P. Epoprostenol and platelet deposition in atherosclerosis. Lancet. 1984 Apr 21;1(8382):905–906. doi: 10.1016/s0140-6736(84)91363-1. [DOI] [PubMed] [Google Scholar]
  19. Sinzinger H., Fitscha P., O'Grady J., Rauscha F., Rogatti W., Vane J. R. Synergistic effect of prostaglandin E1 and isosorbide dinitrate in peripheral vascular disease. Lancet. 1990 Mar 17;335(8690):627–628. doi: 10.1016/0140-6736(90)90412-x. [DOI] [PubMed] [Google Scholar]
  20. Sinzinger H., Kolbe H., Strobl-Jäger E., Höfer R. A simple and safe technique for sterile autologous platelet labelling using "Monovette" vials. Eur J Nucl Med. 1984;9(7):320–322. doi: 10.1007/BF00276462. [DOI] [PubMed] [Google Scholar]
  21. Sinzinger H., Silberbauer K., Kaliman J., Fitscha P. 20 mg aspirin daily--evidence for a clinical future of this extremely low-dose in arterial disease? Vasa. 1988;17(1):10–15. [PubMed] [Google Scholar]
  22. Tateson J. E., Moncada S., Vane J. R. Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins. 1977 Mar;13(3):389–397. doi: 10.1016/0090-6980(77)90019-3. [DOI] [PubMed] [Google Scholar]
  23. Vallance P., Collier J., Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989 Oct 28;2(8670):997–1000. doi: 10.1016/s0140-6736(89)91013-1. [DOI] [PubMed] [Google Scholar]

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