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Thromb Haemost 1998; 79(02): 378-382
DOI: 10.1055/s-0037-1614995
Letters to the Editor
Schattauer GmbH

Effect of Antihypertensive Treatment with Doxazosin on Insulin Sensitivity and Fibrinolytic Parameters

Manfred Zehetgruber
,
Günter Christ
,
Harald Gabriel
,
Gerald Mundigler
,
Renate Beckmann
2   Vascular Biology and Thrombosis Research, University of Vienna, Austria
,
Bernd R. Binder
2   Vascular Biology and Thrombosis Research, University of Vienna, Austria
,
Kurt Huber
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 12. März 1997

Accepted after resubmission 30. September 1997

Publikationsdatum:
08. Dezember 2017 (online)

Auch verfügbar auf
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Summary

The effects of the selective alpha-1-adrenoceptor antagonist doxazosin on metabolic and fibrinolytic parameters were studied in hypertensive patients with various degrees of fasting plasma insulin levels (Group A: 22.5 ± 3 μU/ml, Group B: 8.1 ± 1.5 μU/ml; p <0.01) to disclose a potential link between a doxazosin-induced alteration of insulin and/or lipid metabolism and possible changes of these parameters on the fibrinolytic system. Doxazosin treatment resulted in a dose-dependent reduction of basal insulin levels in group A to 16 ± 3 μU/ml; p <0.05. This finding was paralleled by a dose-dependent increase in t-PAmass concentration in the same patient group (basal t-PAmass from 9.7 ± 1 to 15.5 ± 2 ng/ml; p <0.05). As PAI-1 “active” as well as total antigen levels were not altered in parallel, the net effect on the endogenous fibrinolytic system is an increase of the fibrinolytic potential.

 

  • References

  • 1 Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-607.
    CrossrefPubMedGoogle Scholar
  • 2 Kaplan NM. The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 1989; 149: 1514-20.
    CrossrefPubMedGoogle Scholar
  • 3 Vague P, Juhan-Vague I, Ailaud F, Badier C, Viard R, Alessi MC, Collen D. Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level and relative body weight in normal and obese subjects. Metabolism 1986; 2: 250-3.
    PubMedGoogle Scholar
  • 4 Juhan-Vague I, Alessi MC. Plasminogen activator inhibitor-1 and atherothrombosis. Thromb Haemost 1993; 70: 138-43.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 5 McCormack L, Stickland MH, Grant PJ. Plasminogen activator inhibitor-1 antigen concentration during insulin and oral glucose tolerance tests in obese men. Fibrinolysis 1993; 7: 225-8.
    PubMedGoogle Scholar
  • 6 Mykkänen L, Rönnemaa T, Marniemi J, Haffner SM, Bergman R, Laakso M. Insulin sensitivity is not an independent determinant of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb 1994; 14: 1264-71.
    CrossrefPubMedGoogle Scholar
  • 7 Rocha E, Paramo JA. The relationship between impaired fibrinolysis and coronary heart disease: a role for PAI-1. Fibrinolysis 1994; 8: 294-303.
    PubMedGoogle Scholar
  • 8 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati MB, Catalano M, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, Turri M, PLAT G. Association of increased fibrin turnover and defective fibrinolytic capacity with leg atherosclerosis. Thromb Haemost 1994; 72: 292-6.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 9 Andersson P-E, Johansson J, Berne C. Effect of selective alpha-1 and beta-1-adreno-receptor-blockade on lipoprotein and carbohydrate metabolism in hypertensive subjects, with special emphasis on insulin sensitivity. J Hum Hypertens 1994; 8: 219-26.
    PubMedGoogle Scholar
  • 10 Lehtonen A. and the Finnish Multicenter Study Group Turku, Finland. Doxazosin effects on insulin and glucose in hypertensive patients. Am Heart J 1991; 121: 1307-11.
    CrossrefPubMedGoogle Scholar
  • 11 Kageyama S, Yamamoto J, Mimura A. Doxazosin improves insulin sensitivity in hypertensive patients. Clin Ther 1993; 15: 829-37.
    PubMedGoogle Scholar
  • 12 Westheim A, Daae LNW, Kierulf P. Selective alpha-1-inhibition with doxazosin in hypertensive smokers and non-smokers: haemodynamic and metabolic effects. J Hypertens 1990; 8: 41-6.
    PubMedGoogle Scholar
  • 13 Jansson JH, Johansson B, Boman K, Nilsson TK. Effects of doxazosin and atenolol on the fibrinolytic system in patients with hypertension and elevated serum cholesterol. Eur J Clin Pharmacol 1991; 40: 321-6.
    CrossrefPubMedGoogle Scholar
  • 14 Vague P, Juhan-Vague I, Alessi MC, Badier C, Valadier J. Metformin decreases the high plasminogen activator inhibitor capacity, plasma insulin and triglyceride levels in non diabetic obese subjects. Thromb Haemost 1987; 57: 326-8.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 15 Grant PJ, Stickland MH, Booth NA, Prentice CRM. Metformin causes a reduction in basal and post-venous occlusion plasminogen activator inhibitor-1 in type 2 diabetic patients. Diab Med 1991; 8: 361-5.
    CrossrefPubMedGoogle Scholar
  • 16 Landin K, Tengborn L, Smith U. Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. J Intern Med 1991; 229: 181-7.
    CrossrefPubMedGoogle Scholar
  • 17 JNC- V.. The Fifth Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1993; 153: 154-83.
    CrossrefPubMedGoogle Scholar
  • 18 Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952-7.
    CrossrefPubMedGoogle Scholar
  • 19 Andreotti F, Davies GJ, Hackett DR, Khan MI, De Bart ACW, Aber VR, Maseri A, Kluft C. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. Am J Cardiol 1988; 62: 635-7.
    CrossrefPubMedGoogle Scholar
  • 20 Huber K, Beckmann R, Lang I, Schuster E, Binder BR. Circadian fluctuations in plasma levels of tissue plasminogen activator antigen and plasminogen activator inhibitor activity. Fibrinolysis 1989; 3: 41-3.
    PubMedGoogle Scholar
  • 21 Pollare T, Lithell M, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 1989; 321: 868-73.
    CrossrefPubMedGoogle Scholar
  • 22 Wahlefeld AW. Triglycerides. Determination after enzymatic hydrolysis. In: Methods of enzymatic analysis. Bergmeyer HU. ed. New York: Academic Press; 1979. pp 1831-5.
    Google Scholar
  • 23 Allain CA, Poon LS, Chan CSG. Enzymatic determination of total serum cholesterol. Clin Chem 1974; 20: 470-5.
    PubMedGoogle Scholar
  • 24 Havel RJ, Eder HA, and Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 1955; 34: 1345-53.
    CrossrefPubMedGoogle Scholar
  • 25 Kadish AH, Little RL, Sternberg JC. A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption. Clin Chem 1968; 14: 116-31.
    PubMedGoogle Scholar
  • 26 Hales CN, Randle PJ. Immunoassay of insulin and insulin-antibody precipitate. Biochem J 1963; 88: 137-46.
    CrossrefPubMedGoogle Scholar
  • 27 Korninger C, Speiser W, Wojta J, Binder BR. Sandwich ELISA for t-PA antigen employing a monoclonal antibody. Thromb Res 1986; 41: 527-35.
    CrossrefPubMedGoogle Scholar
  • 28 Wojta J, Holzer M, Hufnagl P, Christ G, Hoover R, Binder BR. Hyperthermia stimulates plasminogen activator inhibitor type 1 expression in human umbilical vein endothelial cells in vitro. Am J Pathol 1991; 139: 911-9.
    PubMedGoogle Scholar
  • 29 Waldo R. Prazosin relieves Raynaud’s vasospasm. JAMA 1979; 241: 1037-40.
    CrossrefPubMedGoogle Scholar
  • 30 Westheim A, Koss A, Sivertssen E. Hemodynamic effects at rest and during exercise in long-term treatment with prazosin in chronic congestive heart failure. Acta Med Scand 1986; 21: 449-53.
    PubMedGoogle Scholar
  • 31 Nilsson IM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-5.
    CrossrefPubMedGoogle Scholar
  • 32 Hamsten A, Wiman B, De Faire U, Blombäck M. Increased levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. New Engl J Med 1985; 313: 1557-63.
    CrossrefPubMedGoogle Scholar
  • 33 Huber K, Resch I, Stefenelli T, Lang I, Probst P, Kaindl F, Binder BR. Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis. Thromb Haemost 1990; 63: 336-9.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 34 Dawson S, Henney A. The status of PAI-1 as a risk factor for arterial and thrombotic disease. Atherosclerosis 1992; 95: 105-17.
    CrossrefPubMedGoogle Scholar
  • 35 Jansson J-H, Olofsson B-O, Nilsson TK. Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease: a 7 year follow-up. Circulation 1993; 88: 2030-4.
    CrossrefPubMedGoogle Scholar
  • 36 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-8.
    CrossrefPubMedGoogle Scholar
  • 37 Wieczorek I, Ludlam CA, Fox KAA. Tissue-type plasminogen activator and plasminogen activator inhibitor activities as predictors of adverse events in unstable angina. Am J Cardiol 1994; 74: 424-9.
    CrossrefPubMedGoogle Scholar
  • 38 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
    CrossrefPubMedGoogle Scholar
  • 39 Juhan-Vague I, Thompsson SG, Jespersen J. on behalf of the ECAT angina pectoris study group. Involvement of the hemostatic system in the insulin resistance syndrome: a study of 1500 patients with angina pectoris. Arterioscler Thromb 1993; 13: 1865-73.
    CrossrefPubMedGoogle Scholar
  • 40 Brown SL, Sobel BE, Fujii S. Attenuation of the synthesis of plasminogen activator inhibitor type-1 by niacin: a potential link between lipid lowering and fibrinolysis. Circulation 1995; 92: 767-72.
    CrossrefPubMedGoogle Scholar