American Journal of Cardiovascular Drugs

, Volume 6, Issue 5, pp 343–348

The Effect of Moxonidine on Endothelial Dysfunction in Metabolic Syndrome

  • Ergun Topal
  • Ayse Sertkaya Cikim
  • Kerim Cikim
  • Ismail Temel
  • Ramazan Ozdemir
Original Research Article



Endothelial dysfunction has been reported in patients with type 2 diabetes mellitus and even in healthy obese individuals with a normal metabolic profile. Sympathetic activity commonly is increased in obese hypertensive patients, and moxonidine is effective in lowering BP and improving insulin sensitivity.


To evaluate the effect of moxonidine on endothelial dysfunction in patients with metabolic syndrome.


Twenty-six patients with mild hypertension were treated with moxonidine and a hypocaloric diet for 3 months, while a second normotensive group (n = 26) were followed-up with calorie restriction alone. Anthropometric (body mass index, waist and hip circumferences, and waist-to-hip ratio) and metabolic features (fasting plasma glucose and insulin, aminotransferases, γ-glutamyl transpeptidase, triglycerides, and cholesterol levels) and flow-mediated dilatation (FMD) were evaluated. Insulin resistance was calculated by using the homeostasis model assessment formula. Insulin sensitivity was calculated according to the quantitative insulin-sensitivity check index (QUICKI).


SBP and DBP (both p < 0.001) and waist circumference (p = 0.02) were higher, and QUICKI (p = 0.043) and FMD (p = 0.01) were lower in the hypertensive group at baseline. After 3 months, nearly all the study parameters improved in both treatment groups. The decrease in BP, increase in FMD, and improvements in metabolic and anthropometric parameters were significantly greater in the moxonidine-treated group than in those treated with diet alone.


Moxonidine is proposed as a valuable option for treating mild-to-moderate hypertension in obese and insulin-resistant patients with metabolic syndrome as it appears to improve endothelial dysfunction in these patients.


  1. 1.
    Zieve FJ. The metabolic syndrome: diagnosis and treatment. Clin Cornerstone 2004; 6 Suppl. 3: S5–13PubMedCrossRefGoogle Scholar
  2. 2.
    Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adults Treatment Panel III). JAMA 2001; 285: 2486–97Google Scholar
  3. 3.
    Anderson PJ, Critchley JA, Chan JC, et al. Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality. Int J Obes Relat Metab Disord 2001; 25: 1782–8PubMedCrossRefGoogle Scholar
  4. 4.
    Nakamura T, Tokunaga K, Shimomura I, et al. Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. Atherosclerosis 1994; 107: 239–46PubMedCrossRefGoogle Scholar
  5. 5.
    Bonora E, Kiechl S, Willeit J, et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 1998; 47: 1643–9PubMedCrossRefGoogle Scholar
  6. 6.
    Nesto RW. The relation of insulin resistance syndromes to risk of cardiovascular disease. Rev Cardiovasc Med 2003; 4(6): 11–8Google Scholar
  7. 7.
    Steinberg HO, Chaker H, Learning R, et al. Obesity/insulin resistance is associated with endothelial dysfunction: implications for the syndrome of insulin resistance. J Clin Invest 1996; 97: 2601–10PubMedCrossRefGoogle Scholar
  8. 8.
    McVeigh GE, Brennan GM, Johnston GD, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (noninsulin-dependent) diabetes mellitus. Diabetologia 1992; 35: 771–6PubMedGoogle Scholar
  9. 9.
    Oflaz H, Ozbey N, Mantar F, et al. Determination of endothelial function and early atherosclerotic changes in healthy obese women. Diabetes Nutr Metab 2003; 16: 176–81PubMedGoogle Scholar
  10. 10.
    Hamdy O, Ledbury S, Mullooly C, et al. Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome. Diabetes Care 2003; 26: 2119–25PubMedCrossRefGoogle Scholar
  11. 11.
    Cersosimo E, Defronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev. Epub 2006 Feb 28Google Scholar
  12. 12.
    Wheatcroft SB, Williams IL, Shah AM, et al. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med 2003; 20(4): 255–68PubMedCrossRefGoogle Scholar
  13. 13.
    Williams IL, Chowienczyk PJ, Wheatcroft SB, et al. Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans. Diabetes Obes Metab 2006; 8(3): 296–301PubMedCrossRefGoogle Scholar
  14. 14.
    Landsberg L. Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why. J Hypertens 2001; 19: 523–8PubMedCrossRefGoogle Scholar
  15. 15.
    Esler M, Rumantir M, Wiesner G, et al. Sympathetic nervous system and insulin resistance: from obesity to diabetes. Am J Hypertens 2001; 14: 304S–9SPubMedCrossRefGoogle Scholar
  16. 16.
    Lithell O. Insulin resistance and diabetes in the context of treatment of hypertension. Blood Press 1998; Suppl. 3: 28–31Google Scholar
  17. 17.
    Haenni A, Lithell H. Moxonidine improves insulin sensitivity in insulin-resistant hypertensives. J Hypertens Suppl 1999; 17: 29–35Google Scholar
  18. 18.
    Sanjuliani AF, de Abreu VG, Francischetti EA. Selective imidazoline agonist moxonidine in obese hypertensive patients. Int J Clin Pract 2006; 60(5): 621–9PubMedCrossRefGoogle Scholar
  19. 19.
    Chazova I, Almazov VA, Shlyakhto E. Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin. Diabetes Obes Metab 2006; 8(4): 456–65PubMedCrossRefGoogle Scholar
  20. 20.
    Kaaja RJ, Poyhonen-Alho MK. Insulin resistance and sympathetic overactivity in women. J Hypertens 2006; 24(1): 43–5CrossRefGoogle Scholar
  21. 21.
    Seidell JC, Deurenberg P, Hautvast JGAJ. Obesity and fat distribution in relation to health: Current insights and recommendations. World Rev Nutr Diet 1987; 50: 57–91PubMedGoogle Scholar
  22. 22.
    Vanhala MJ, Pitkajarvi TK, Kumpusalo EA, et al. Obesity type and clustering of insulin resistance associated cardiovascular risk factors in middle aged men and women. Int J Obes 1988; 22: 369–74CrossRefGoogle Scholar
  23. 23.
    Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetes 1985; 28: 412–9Google Scholar
  24. 24.
    Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402–10PubMedCrossRefGoogle Scholar
  25. 25.
    Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–5PubMedCrossRefGoogle Scholar
  26. 26.
    Corretti MC, Anderson TJ, Benjamin EJ, et al. International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelialdependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257–65PubMedCrossRefGoogle Scholar
  27. 27.
    Riccardi G, Rivellese AA. Dietary treatment of the metabolic syndrome: the optimal diet. Br J Nutr 2000; 83 Suppl. 1: 143–8CrossRefGoogle Scholar
  28. 28.
    Lichtenstein AH, Kennedy E, Barrier P, et al. Dietary fat consumption and health. Nutr Rev 1998; 56: S3–19PubMedCrossRefGoogle Scholar
  29. 29.
    Ziegler D, Haxhiu MA, Kaan EC, et al. Pharmacology of moxonidine, an I-1 imidazoline receptor agonist. J Cardiovasc Pharmacol 1996; 27 Suppl. 3: 26–37CrossRefGoogle Scholar
  30. 30.
    Reis DJ. Neurons and receptors in the rostroventrolateral medulla mediating the antihypertensive actions of drugs acting at imidazoline receptors. J Cardiovasc Pharmacol 1996; 27 Suppl. 3: 11–8CrossRefGoogle Scholar
  31. 31.
    Abellan J, Leal M, Hernandez-Menarguez F, et al. Efficacy of moxonidine in the treatment of hypertension in obese, noncontrolled hypertensive patients. Kidney Int Suppl 2005; (93): 20-Google Scholar
  32. 32.
    van Zwieten PA. From alpha and beta to I1: an overview of sympathetic receptors involved in blood pressure control targets for drug treatment. J Cardiovasc Pharmacol 1996; 27 Suppl. 3: 5–10CrossRefGoogle Scholar
  33. 33.
    Sharma AM, Wagner T, Marsalek P. Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study. J Hum Hypertens 2004; 18(9): 669–75PubMedCrossRefGoogle Scholar
  34. 34.
    Carr DB, Utzschneider KM, Hull RL, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes 2004; 53: 2087–94PubMedCrossRefGoogle Scholar
  35. 35.
    Pouliot MC, Després JP, Lemieux S, et al. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994; 73: 460–8PubMedCrossRefGoogle Scholar
  36. 36.
    International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. April 14, 2005 [online]. Available from URL: [Accessed 2005 Jun 10]
  37. 37.
    Alberti KG, Zimmet P, Shaw J. The metabolic syndrome: a new worldwide definition. Lancet 2005; 366: 1059–62PubMedCrossRefGoogle Scholar
  38. 38.
    Lavrencic A, Salobir BG, Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Biol 2000; 20: 551–5CrossRefGoogle Scholar
  39. 39.
    Sakamoto S, Minami K, Niwa Y, et al. Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, model of spontaneous NIDDM. Diabetes 1998; 47: 82–6PubMedCrossRefGoogle Scholar
  40. 40.
    Panza JA, Quyyumi AA, Brush Jr JE, et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990; 323: 22–7PubMedCrossRefGoogle Scholar
  41. 41.
    Laine H, Yuki-Jarvinen H, Kirvela O, et al. Insulin resistance of glucose uptake in skeletal muscle cannot be ameliorated by enhancing endothelium-dependent blood flow in obesity. J Clin Invest 1998; 101: 1156–62PubMedCrossRefGoogle Scholar
  42. 42.
    Higashi Y, Sasaki S, Nakagawa K, et al. Effect of obesity on endotheliumdependent, nitric oxide-mediated vasodilation in normotensive individuals and patients with essential hypertension. Am J Hypertens 2001; 14: 1038–45PubMedCrossRefGoogle Scholar
  43. 43.
    Gairard A, Lopez-Miranda V, Pernot F, et al. Effect of i1 imidazoline receptor agonist, moxonidine, in nitric oxide-deficient hypertension in pregnant rats. J Cardiovasc Pharmacol 2004; 43: 731–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Ergun Topal
    • 1
  • Ayse Sertkaya Cikim
    • 2
  • Kerim Cikim
    • 3
  • Ismail Temel
    • 4
  • Ramazan Ozdemir
    • 1
  1. 1.Department of CardiologyInonu University Faculty of MedicineMalatyaTurkey
  2. 2.Department of Internal Medicine, Division of Endocrinology and MetabolismInonu University Faculty of MedicineMalatyaTurkey
  3. 3.Department of Internal MedicineInonu University Faculty of MedicineMalatyaTurkey
  4. 4.Department of BiochemistryInonu University Faculty of MedicineMalatyaTurkey

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