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Hypertension Research
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Comparison of the Effects of Valsartan and Felodipine on Plasma Leptin and Insulin Sensitivity in Hypertensive Obese Patients
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  • Original Article
  • Published: 01 March 2005

Comparison of the Effects of Valsartan and Felodipine on Plasma Leptin and Insulin Sensitivity in Hypertensive Obese Patients

  • Roberto Fogari1,
  • Giuseppe Derosa1,
  • Annalisa Zoppi1,
  • Andrea Rinaldi1,
  • Pierangelo Lazzari1,
  • Elena Fogari1,
  • Amedeo Mugellini1 &
  • …
  • Paola Preti1 

Hypertension Research volume 28, pages 209–214 (2005)Cite this article

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Abstract

Aim of this study was to compare the effect of valsartan and felodipine on blood pressure (BP), plasma leptin (L), insulin sensitivity and plasma norepinephrine (NE) in obese hypertensive patients. Ninty-six obese patients (body mass index [BMI] ≥30 kg/m2) with mild to moderate essential hypertension (diastolic blood pressure [DBP] >90 and <110 mmHg, as evaluated with an appropriately sized cuff) aged 31–60 years, were randomized to a valsartan (80 mg/day for 16 weeks; n=48) or felodipine (5 mg/day for 16 weeks; n=48) treatment group after a 2-week wash-out period. After the first 4 weeks of treatment there was a titration with dose-doubling in non responder patients (DBP > 90 mmHg). At the end of the placebo period and of active treatment period, BP and BMI were evaluated and a venous sample was drawn at the same hour in the morning to evaluate plasma L and NE. Insulin resistance index (HOMA-IR) was calculated. No dietary advice was prescribed. Both valsartan and felodipine significantly decreased BP values (-19.3/15 mmHg and -18.9/13.6 mmHg, respectively p<0.001 vs. placebo), with no difference between treatments. However, felodipine increased plasma NE (+124 pg/ml, +38.2%, p<0.05 vs. placebo and <0.01 vs. valsartan) and had no effect on L, body weight and HOMA-IR index, while valsartan did not modify NE and produced a significant reduction in L (-3.7 ng/ml, -10.1%, p<0.05 vs. placebo), BMI (-1.7 kg/m2, -4.7%, p<0.01 vs. placebo) and HOMA-IR index (-1.6, -20%, p<0.05 vs. placebo). These results suggest that in hypertensive obese subjects, treatment with valsartan might offer an advantage over treatment with felodipine, since valsartan may help to improve obesity-related disorders in addition to lowering BP.

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References

  1. National Institute of Health : Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults: the Evidence Report (NIH publication 98–4083). Bethesda, National Institutes of Health, 1998, pp 7–33.

  2. Visscher TL, Seidell JC : The public health impact of obesity. Annu Rev Public Health 2001; 22: 355–375.

    Article  CAS  PubMed  Google Scholar 

  3. McLellan F : Obesity rising to alarming levels around the world. Lancet 2002; 359: 1412.

    Article  PubMed  Google Scholar 

  4. Kenchaiah S, Evans JC, Levy D, et al: Obesity and the risk of heart failure. N Engl J Med 2002; 347: 305–313.

    Article  PubMed  Google Scholar 

  5. Eckel RH, Krauss RM, for the AHA Nutrition Committee : American Heart Association call to action: obesity as a major risk factor for coronary heart disease. Circulation 1998; 97: 2099–2100.

    Article  CAS  PubMed  Google Scholar 

  6. Grundy SM : Obesity, metabolic syndrome and coronary atherosclerosis. Circulation 2002; 105: 2696–2698.

    Article  PubMed  Google Scholar 

  7. Sowers JR : Obesity as a cardiovascular risk factor. Am J Med 2003; 115 ( Suppl 8A): 37S–41S.

    Article  CAS  PubMed  Google Scholar 

  8. Schuldner AR, Yang R, Gong DW : Resistin, obesity and insulin resistance: the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001; 345: 1345–1346.

    Article  Google Scholar 

  9. Misra A, Garg A : Leptin: its receptor and obesity. J Invest Med 1996; 44: 540–548.

    CAS  Google Scholar 

  10. Nakagawa K, Higashi Y, Sasaki S, Oshima T, Matsuura H, Chayama K : Leptin causes vasodilation in humans. Hypertens Res 2002; 25: 161–165.

    Article  CAS  PubMed  Google Scholar 

  11. Barba G, Russo O, Siani A, et al: Plasma leptin and blood pressure in men: graded associaton independent of body mass and fat pattern. Obes Res 2003; 11: 160–166.

    Article  PubMed  Google Scholar 

  12. Eikelis N, Schlaich M, Aggarwal A, Kaye D, Esler M : Interactions between leptin and the human sympathetic nervous system. Hypertension 2003; 41: 1072–1079.

    Article  CAS  PubMed  Google Scholar 

  13. Guha PK, Villareal D, Reams GP, Freeman RH : Role of leptin in the regulation of body fluid volume and pressures. Am J Ther 2003; 10: 211–218.

    Article  PubMed  Google Scholar 

  14. Rahmouni K, Haynes WG : Leptin and the cardiovascular system. Recent Prog Horm Res 2004; 59: 225–244.

    Article  CAS  PubMed  Google Scholar 

  15. Aneja A, El-Atat F, McFarlane SI, Sowers JR : Hypertension and obesity. Recent Prog Horm Res 2004; 59: 169–205.

    Article  CAS  PubMed  Google Scholar 

  16. Matsuda K, Teragawa H, Fukuda Y, Nakagawa K, Higashi Y, Chayama K : Leptin causes nitric-oxide independent coronary artery vasodilation in humans. Hypertens Res 2003; 26: 147–152.

    Article  CAS  PubMed  Google Scholar 

  17. Hall JE : The kidney, hypertension and obesity. Hypertension 2003; 41: 625–633.

    Article  PubMed  CAS  Google Scholar 

  18. Ferrannini E, Natali A : Essential hypertension, metabolic disorders and insulin resistance. Am Heart J 1991; 121: 1274–1282.

    Article  CAS  PubMed  Google Scholar 

  19. Imazu M : Hypertension and insulin disorders. Curr Hypertens Rep 2002; 6: 477–482.

    Article  Google Scholar 

  20. Nishina M, Kikichi T, Yamazaki H, Kameda K, Hiura M, Uchiyama M : Relationship among systolic blood pressure, serum insulin and leptin, and visceral fat accumulation in obese children. Hypertens Res 2003; 26: 281–288.

    Article  CAS  PubMed  Google Scholar 

  21. Remie R, Zaagsma J : A new technique for the study of vascular presynaptic receptors in freely moving rats. Heart Circ Physiol 1986; 251: 4463–4467.

    Google Scholar 

  22. Hjemdahl P : Plasma catecholamines as markers for sympatho-adrenal activity in human primary hypertension. Pharmacol Toxicol 1988; 63 ( Suppl 1): 27–31.

    Article  PubMed  Google Scholar 

  23. Umeda M, Kanda T, Murakami M : Effects of angiotensin II receptor antagonists on insulin resistance syndrome and leptin in sucrose-fed spontaneously hypertensive rats. Hypertens Res 2003; 26: 485–492.

    Article  CAS  PubMed  Google Scholar 

  24. Ficek J, Kokot F, Chudek J, Adamczak M, Ficek R, Wiecek A : Influence of antihypertensive treatment with perindopril, pindolol or felodipine on plasma leptin concentration in patients with essential hypertension. Horm Metab Res 2002; 34: 703–708.

    Article  CAS  PubMed  Google Scholar 

  25. Marckham A, Goa KL : Valsartan. A review of its pharmacology and therapeutic use in essential hypertension. Drugs 1997; 54: 299–311.

    Article  Google Scholar 

  26. Saltiel E, Gray Ellrodt A, Monk JP, Langley MS : Felodipine: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension. Drugs 1988; 36: 387–428.

    Article  CAS  PubMed  Google Scholar 

  27. Remie R, Zaagsma J : A new technique for the study of vascular presynaptic receptors in freely moving rats. Heart Circ Physiol 1986; 251: 4463–4467.

    Google Scholar 

  28. Hjemdahl P : Plasma catecholamines as markers for sympatho-adrenal activity in human primary hypertension. Pharmacol Toxicol 1988; 63 ( Suppl 1): 27–31.

    Article  PubMed  Google Scholar 

  29. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC : Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  PubMed  Google Scholar 

  30. Lansang MC, Williams GH, Carrol J : Correlation between the glucose clamp technique and the Homeostasis Model Assessment in hypertension. Am J Hypertens 2001; 14: 51–53.

    Article  CAS  PubMed  Google Scholar 

  31. Parhami F, Tintut Y, Ballard A, et al: Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. Circ Res 2001; 88: 954–960.

    Article  CAS  PubMed  Google Scholar 

  32. Oda A, Taniguchi T, Yokoyama M : Leptin stimulates rat aortic smooth muscle cell proliferation and migration. Kobe J Med Sci 2001; 47: 141–150.

    CAS  PubMed  Google Scholar 

  33. Singhal A, Farooqi IS, Cole TJ, et al: Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease. Circulation 2002; 106: 1919–1924.

    Article  CAS  PubMed  Google Scholar 

  34. Kuwamura T, Yoshida K, Sugawara A, et al: Impact of exercise and angiotensin converting enzyme inhibition on tumor necrois factor-α and leptin in fructose-fed hypertensive rats. Hypertens Res 2002; 25: 927–938.

    Article  Google Scholar 

  35. Barton M, Carmona R, Ortmann J, Krieger JE, Traupe T : Obesity-associated activation of angiotensin and endothelin in the cardiovascular system. Int J Biochem Cell Biol 2003; 35: 826–837.

    Article  CAS  PubMed  Google Scholar 

  36. Ailhaud G, Fukamizu A, Massiera F, Negrel R, Saint-Mark P, Teboul M : Angiotensinogen, angiotensin II and adipose tissue development. Int J Obes Relat Metab Disord 2000; 24 ( Suppl 4): S33–S35.

    Article  CAS  PubMed  Google Scholar 

  37. Giacchetti G, Falcia E, Falcia, et al: Gene expression of angiotensinogen in adipose tissue of obese patients. Int J Obes Relat Metab Disord 2000; 24 ( Suppl 2): S142–S143.

    Article  CAS  PubMed  Google Scholar 

  38. Laakso M, Karjalaainen L, Lempiainen-Kuosa P : Effects of losartan on insulin sensitivity in hypertensive subjects. Hypertension 1996; 28: 392–396.

    Article  CAS  PubMed  Google Scholar 

  39. Moan A, Hoieggen A, Seljeflot I, Risanger T, Arnesen H, Kjeldsen SE : The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity. J Hypertens 1996; 14: 1093–1097.

    Article  CAS  PubMed  Google Scholar 

  40. Fogari R, Zoppi A, Corradi L, Lazzari P, Mugellini A, Lusardi P : Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients. Br J Clin Pharmacol 1998; 46: 467–471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Iimura O, Shimamoto K, Matsuda K, et al: Effects of angiotensin receptor antagonist and angiotensin converting enzyme inhibitor on insulin sensitivity in fructose fed hypertensive rats and essential hypertensives. Am J Hypertens 1995; 8: 353–357.

    Article  CAS  PubMed  Google Scholar 

  42. Moan A, Hoieggen A, Nordby G, Eide IK, Kjeldsen SE : Effects of losartan on insulin sensitivity in severe hypertension: connections through sympathetic nervous system activity. J Hum Hypertens 1995; 9 ( Suppl 5): S45–S50.

    PubMed  Google Scholar 

  43. Leenen FH, Holliwell D : Antihypertensive effect of felodipine associated with persistent sympathetic activation and minimal regression of left ventricular hypertrophy. Am J Cardiol 1992; 69: 639–645.

    Article  CAS  PubMed  Google Scholar 

  44. Hjemdahl P, Wallen NH : Calcium antagonist treatment, sympathetic activity and platelet function. Eur Heart J 1997; 18 ( Suppl A): A36–A50.

    Article  CAS  PubMed  Google Scholar 

  45. Fogari R, Zoppi A, Corradi L, Preti P, Malamani GD, Mugellini A : Effects of different dihydropyridine calcium antagonists on plasma norepinephrine in essential hypertension. J Hypertens 2000; 18: 1871–1875.

    Article  CAS  PubMed  Google Scholar 

  46. Grassi G, Esler M : How to assess sympathetic activity in humans. J Hypertens 1999; 17: 719–734.

    Article  CAS  PubMed  Google Scholar 

  47. Mancia G, Grassi G, Giannattasio C, Serravalle G : Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 1999; 34: 724–728.

    Article  CAS  PubMed  Google Scholar 

  48. Palatini P : Sympathetic overactivity in hypertension: a risk factor for cardiovascular disease. Curr Hypertens Rep 2001; 3 ( Suppl 1): S3–S9.

    Article  PubMed  Google Scholar 

  49. Itoh K, Imai K, Masuda T, et al: Weight loss in obese subjects reduced blood pressure and the norepinephrine excretion in only hypertensive group. J Hypertens 1998; 16 ( Suppl 2): S152.

    Google Scholar 

  50. Klein S, Coppack SW, Mohamed-Ali V, Landt M : Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes 1996; 45: 984–987.

    Article  CAS  PubMed  Google Scholar 

  51. Van Harmelen V, Reynisdottiv S, Eriksson P, et al: Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998; 47: 913–917.

    Article  CAS  PubMed  Google Scholar 

  52. Considine RV, Sinha MK, Heiman MI, et al: Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334; 292–295.

    Article  CAS  PubMed  Google Scholar 

  53. Segal KR, Landt M, Klein S : Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 1996; 45: 988–991.

    Article  CAS  PubMed  Google Scholar 

  54. Mohamed-Ali V, Pinkney JH, Panahloo A, et al: Relationships between plasma leptin and insulin concentrations, but not insulin resistance, in non-insulin-dependent (Type 2) diabetes mellitus. Diabet Med 1997; 14: 376–380.

    Article  CAS  PubMed  Google Scholar 

  55. Agata J, Masuda A, Takeda M, et al: High plasma immunoreactive leptin level in essential hypertension. Am J Hypertens 1997; 10: 1171–1174.

    Article  CAS  PubMed  Google Scholar 

  56. Itoh K, Imai K, Masuda T, et al: Relationship between changes in serum leptin levels and blood pressure after weight loss. Hypertens Res 2002; 25: 881–886.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine and Therapeutics, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy

    Roberto Fogari, Giuseppe Derosa, Annalisa Zoppi, Andrea Rinaldi, Pierangelo Lazzari, Elena Fogari, Amedeo Mugellini & Paola Preti

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Correspondence to Roberto Fogari.

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Fogari, R., Derosa, G., Zoppi, A. et al. Comparison of the Effects of Valsartan and Felodipine on Plasma Leptin and Insulin Sensitivity in Hypertensive Obese Patients. Hypertens Res 28, 209–214 (2005). https://doi.org/10.1291/hypres.28.209

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  • Received: 06 October 2004

  • Accepted: 07 December 2004

  • Issue date: 01 March 2005

  • DOI: https://doi.org/10.1291/hypres.28.209

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Keywords

  • valsartan
  • leptin
  • insulin sensitivity
  • hypertension
  • obesity

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