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Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors

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Summary

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96–104 mmHg without (EH, n=12) or with other risk factors (EH+S, n=12, EH+DM, n=12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.

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References

  1. Smith WM. Epidemiology of hypertension.Med Clin North Am 1977;61:467–486.

    PubMed  Google Scholar 

  2. Kannel WB, Sorlie P. Hypertension in Framingham. In: Paul O, ed.Epidemiology and Control of Hypertension. Miami: Symposia Specialists, 1975:553–592.

    Google Scholar 

  3. Wilhelmsen L. Synergistic effects of risk factors.Clin Exp Hypertens A 1990;12:845–863.

    PubMed  Google Scholar 

  4. Stokes J, Kannel WB, Wolf PA, et al. The relative importance of selected risk factors for various manifestations of cardiovascular disease among men and women from 35 to 64 years old: 30 years of follow-up in the Framingham Study.Circulation 1987;75(Suppl 5):65–73.

    Google Scholar 

  5. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: Principal results.Br Med J 1985;291:97–104.

    Google Scholar 

  6. Stamler J, Berkson DM, Lindberg HA. Risk factors: Their role in the etiology and pathogenesis of the atherosclerotic diseases. In: Wissler RW, Geer JC, eds.The Pathogenesis of Atherosclerosis. Baltimore, MD: Williams & Wilkins 1972:41–119.

    Google Scholar 

  7. De Clerk F. Review: Blood platelets in human essential hypertension.Agents Actions 1986;18:5–6.

    PubMed  Google Scholar 

  8. Landin K, Tengborn L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease.J Intern Med 1990;227:273–278.

    PubMed  Google Scholar 

  9. Kjeldsen S, Gjesdal K, Eide I, Aakeson I, Amundsen R, Foss OP, Leren P. Increased β-thromboglobulin in essential hypertension: Interactions between arterial plasma adrenaline, platelet function and blood lipids.Acta Med Scand 1983;213:369–373.

    PubMed  Google Scholar 

  10. Belch JJF, McArdle BM, Burns P, Lowe GDO, Forbes CD. The effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in habitual smokers.Thromb Haemost 1984;51:6–8.

    PubMed  Google Scholar 

  11. Haire WD, Goldsmith JC, Rasmussen J. Abnormal fibrinolysis in healthy male cigarette smokers: Role of plasminogen activator inhibitors.Am J Hematol 1989;31;36–40.

    PubMed  Google Scholar 

  12. Alessandrini P, McRae J, Feman S, Fitzgerald GA. Thromboxane biosynthesis and platelet function in type I diabetes mellitus.N Engl J Med 1988;319;208–212.

    PubMed  Google Scholar 

  13. Juhan-Vague I, Roul C, Alessi MC, et al. Increased plasminogen activator inhibitor activity in non-insulin dependent diabetic patients—relationship with plasma insulin.Thromb Haemost 1989;61:370–373.

    PubMed  Google Scholar 

  14. Juhan-Vague I, Valadier J, Alessi MC, et al. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis.Thromb Haemost 1987;57:67–72.

    PubMed  Google Scholar 

  15. Dawson S, Henney A. The status of PAI-1 as a risk factor for arterial and thrombotic disease: A review.Atherosclerosis 1992;95:105–117.

    PubMed  Google Scholar 

  16. Winther K. The effects of β-blockade on platelet function and fibrinolytic activity.J Cardiovasc Pharmacol 1987; 10(Suppl 2):94–98.

    Google Scholar 

  17. Birkebaek NH, Vejby-Christen H, Jakobsen P, Winther K. The effect of nifedipine and captopril on platelet activation and prostanoid production in essential hypertension.J Hypertens 1988;6(Suppl 4):S378-S380.

    Google Scholar 

  18. Mehta J, Mehta P, Ostrowski N, Crews F. Effects of verapamil on platelet aggregation, ATP release and thromboxane generation.Thromb Res 1983;30:468–475.

    Google Scholar 

  19. Winther K, Gleerup G, Hedner T. Enhanced risk of thromboembolic disease in hypertension from platelet hyperfunction and decreased fibrinolytic activity: Has antihypertensive therapy any influence?J Cardiovasc Pharmacol 1992; 19(Suppl 3):S21-S24.

    Google Scholar 

  20. Ding Y, Han C, Chou TC, Lai WY, Shiao MF. Effects of the calcium antagonist isradipine on 24-hour ambulatory blood pressure, platelet aggregation, and neutrophil oxygen free radicals in hypertension.J Cardiovasc Pharmacol 1992; 19(Suppl 3):S32-S37.

    PubMed  Google Scholar 

  21. Kirchhof B, Kirchhof U, Etscheid G. Attempts to standardize platelet aggregation measurements: Simplified screening tests.Haemostatis 1990;20:169–180.

    Google Scholar 

  22. Born GVR. Aggregation of blood platelets by adenosine disphosphate and its reversal.Nature 1962;927–929.

  23. Letter to the editor: Measurements of platelet factor 4 and β-thromboglobulin by an enzyme-linked immunosorbent assay.Clin Chim Acta 1988;175:113–114.

    Google Scholar 

  24. Grimaudo V, Hauert J, Bachmann F, Kruithof EKO. Diurnal variation of the fibrinolytic system.Thromb Haemost 1988;59:495–499.

    PubMed  Google Scholar 

  25. Nyrop M, Zweifler AJ. Platelet aggregation in hypertension and the effects of antihypertensive treatment.J Hypertens 1988;6:263–269.

    PubMed  Google Scholar 

  26. Gleerup G, Winther K. Decreased fibrinolytic activity and increased platelet function in hypertension: Possible influence of calcium antagonism.Am J Hypertens 1991;4: 168S-171S.

    PubMed  Google Scholar 

  27. Smith U, Gudbjornsdottir S, Landin K. Hypertension as a metabolic disorder—an overview.J Intern Med 1991; 229(Suppl 2):1–7.

    PubMed  Google Scholar 

  28. MacMahon S, Peto R, Cutier J, et al. Blood pressure, stroke and coronary heart disease. Part 1. Prolonged difference in blood pressure: Prospective observational studies corrected for the regression dilution bias.Lancet 1990;i:765–774.

    Google Scholar 

  29. Wolf PA, Dawber TR, Thomas EH, Cotton T, Nickson RJ. The epidemiology of atherothrombotic brain infarction (ABI): The Framingham Study.Stroke 1977;8:4–9.

    Google Scholar 

  30. Meade TW, Chakrabarti R, Hainsen AP, North WRS, Stirling Y. Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations.Br Med J 1979;20: 153–156.

    Google Scholar 

  31. Auwerx J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen activator inhibitor in diabetes mellitus.Arteriosclerosis 1988;8:68–72.

    PubMed  Google Scholar 

  32. Sagel J, Colwell JA, Crook L. Lamins M. Increased platelet aggregation in early diabetes mellitus.Ann Intern Med 1975;82:733–738.

    PubMed  Google Scholar 

  33. Colwell JA, Halushka PV, Sarji K, Levine J, Sagel J, Nair RMG. Altered platelet function in diabetes mellitus.Diabetes 1976;25:826–31.

    PubMed  Google Scholar 

  34. Gleerup G, Hedner T, Hjorting Hansen E, Winther K. Does antihypertensive therapy affect the natural protection against thrombosis?J Cardiovasc Pharmacol 1991;18(Suppl 3):S34-S36.

    Google Scholar 

  35. Ding Y, Han C, Chou T, Lai W, Shiao M. Effect of isradipine on platelet aggregation and oxygen free radicals in hypertension.J Hypertens 1991;9(Suppl 6):S370-S371.

    Google Scholar 

  36. Sinziger H, Virgolini I, Rauscha F, Fitscha P, Grady JO. Isradipine improves platelet function in hypertensives.Eur J Clin Pharmacol 1992;42:43–46.

    PubMed  Google Scholar 

  37. Weiss K, Fitscha P, Grady JO, Sinziger H. Isradipine: A potent calcium blocker with beneficial effects on platelet function and vascular prostacyclin production.Thromb Res 1989;54:311–317.

    PubMed  Google Scholar 

  38. Sinziger H, Virgolini I, Grady JO, et al. Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine.Eicosanoids 1992;5:13–16.

    PubMed  Google Scholar 

  39. Muiesan G, Agabiti E, Muiesan ML, Castellano M, Beschi M. Adrenergic activity and left ventricular function during treatment of essential hypertension with calcium antagonist.Am J Cardiol 1986;57:44D-49D.

    PubMed  Google Scholar 

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Ranieri, G., Filitti, V., Andriani, A. et al. Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors. Cardiovasc Drug Ther 10, 119–123 (1996). https://doi.org/10.1007/BF00823589

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  • DOI: https://doi.org/10.1007/BF00823589

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