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Molecular and Cellular Biochemistry

, Volume 282, Issue 1–2, pp 187–191 | Cite as

The effect of systemic leptin administration on aorta smooth muscle responses in diabetic rats

  • Çiğdem Özer
  • Şebnem Gülen
  • Ergin Dileköz
  • Aydan Babül
  • Z. Sevim Ercan
Article

Abstract

Leptin produces effects in central nervous system and peripheral tissues via its specific receptors. Leptin also stimulates nitric oxide release in a concentration-dependent manner. In this study, our aim was to test the hypothesis that whether leptin has a modulatory role on endothelium or smooth muscle function in streptozotocin (STZ)-induced diabetic rats. Wistar-Albino rats were divided into four groups: 1 – Control, 2 – Diabetic, 3 – Control + leptin and 4 – Diabetic + leptin. Experimental diabetes was produced by intraperitoneal injection of a single dose of STZ (55 mg/kg). Diabetes was determined by increased fasting blood glucose level on the 7th day of the experiment. Leptin (0.1 mg/kg/day) was administered intraperitoneally for 5 days. At the end of the 5th day, thoracic aortas were isolated and phenylephrine (Phe)-induced contractions and acetylcholine (ACh)-induced relaxations of each group were estimated. In diabetic rats, Phe-induced contractility was increased (p < 0.05). Leptin pre-treatment increased the Phe-induced contractility significantly in aortic rings obtained from diabetic rats (p < 0.05). In normal rats, leptin administration produced only a slight and non-significant increase in Phe-induced contractions. Although the relaxant responses were decreased in diabetic rats, leptin administration enhanced the ACh-induced relaxation in both normal and diabetic animals significantly. As a conclusion; chronic leptin pre-treatment caused a significant increase both in Phe-induced contractions and ACh-induced Endothelial-Derived Relaxing Factor (EDRF)/Nitric oxide-mediated relaxations in the aortic rings isolated from streptozotocin-induced diabetic rats. This peptide hormone caused a significant increase in the relaxations obtained by ACh while not inducing a significant alteration in the contractile effect of Phe in control rats.

Key words

aorta diabetes leptin streptozotocin 

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References

  1. 1.
    Parhami F, Tintut Y, Ballard A, Fogelman AM, Demer L: Leptin enhaces the calcification of vascular cells: artery wall as a target of leptin. Circ Res 88(9): 954–960, 2001PubMedCrossRefGoogle Scholar
  2. 2.
    Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540–543, 1995PubMedCrossRefGoogle Scholar
  3. 3.
    Schwartz MW, Seeley RJ, Ampfield LA, Burn P, Baskin DG: Identification of targets of leptin action in rat hypothalamus. J Clin Invest 98: 1101–1106, 1996PubMedCrossRefGoogle Scholar
  4. 4.
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432, 1994PubMedCrossRefGoogle Scholar
  5. 5.
    Levin N, Nelson C, Gurney A, Vandlen R, de Sauvage F: decreased food intake does not completely account for adiposity reduction after ob protein infusion. Proc Natl Acad Sci USA 93: 1726–1730, 1996CrossRefPubMedGoogle Scholar
  6. 6.
    Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415: 339–343, 2002CrossRefPubMedGoogle Scholar
  7. 7.
    Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgins LC, Ntambi JM: Role of stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297: 240–243, 2002PubMedCrossRefGoogle Scholar
  8. 8.
    Seufert J: Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 53(1): 152–158, 2004CrossRefGoogle Scholar
  9. 9.
    Shek EW, Brands MW, Hall JE: Hypertension Jan;31(1 Pt 2): 409–414, 1998Google Scholar
  10. 10.
    Dunbar JC, Hu Y, Lu H: Intracerebroventricular leptin, increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 46: 2040–2043, 1997PubMedCrossRefGoogle Scholar
  11. 11.
    Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL: Receptor-mediated regional sympathetic nerve actions by leptin. J Clin Invest 100: 1–9, 1997CrossRefGoogle Scholar
  12. 12.
    Lohn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM: Periadventitial fat releases a vascular relaxing factor. Faseb J 16(9): 1057–1063, 2002CrossRefPubMedGoogle Scholar
  13. 13.
    Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, Floreres Riveros JR: Biological action of leptin as an angiogenic factor. Nature 281: 1683–1686, 1998Google Scholar
  14. 14.
    Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, Amati G, Trimarco B: Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 49: 293–297, 2000PubMedCrossRefGoogle Scholar
  15. 15.
    Vecchione C, Aretini A, Maffei A, Marino G, Selvetella G, Poulet R, Trimarco V, Frati G, Lembo G: Cooperation between insulin and leptin in the modulatin of vascular tone. Hypertension 42: 166–170, 2003CrossRefPubMedGoogle Scholar
  16. 16.
    Frunhberk G: Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 48(4): 903–908, 1999CrossRefGoogle Scholar
  17. 17.
    Szkudelski T: The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50: 536–546, 2001Google Scholar
  18. 18.
    Francis J, Mohankumar SMJ, Quadri SK: Systemic administration of lipopolysaccharide increases plasma leptin levels. Endocrine 10: 291–295, 1999PubMedCrossRefGoogle Scholar
  19. 19.
    Wauters M, Considine VR, van Gaal LF: Human leptin: from an adipocyte hormone to an endocrine mediator. Euro J Endocr 143: 293–311, 2000CrossRefGoogle Scholar
  20. 20.
    Hintz K, Aberle NS, Ren J: Insulin resistance induces hyperleptinemia, cardiac contractile dysfunction but not cardiac leptin resistance in ventricular myocytes. Int J Obes Relat Metab Disord Oct 27(10): 1196–1203, 2003CrossRefGoogle Scholar
  21. 21.
    Kennel WB, Brand N, Skinner JJ, Dauber TR, McNamara PM: The relation of adiposity to blood pressure and development of hypertension: the Framingram study. Ann Intern Med 67: 48–59, 1967Google Scholar
  22. 22.
    Manson JE, Willet WC, Stampfer MJ, Colditz GA, Hunter DJ, Hankinson SE, Hennekens CH, Speizer FE: Body weight and mortality among women. N Engl J Med 333: 677–685, 1995CrossRefPubMedGoogle Scholar
  23. 23.
    Weber LP, Macleod KM: Influence of streptozotocin diabetes on the alpha-1 adrenoceptor and asssociated G proteins in rat arteries. J Pharmacol Exp Ther 283: 1469–1478, 1997PubMedGoogle Scholar
  24. 24.
    Fortuno A, Rodriguez A, Gomez-Ambrosi J, Muniz P, Salvador J, Diez J, Fruhbeck G: Leptin inhibitis angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta. Endocrinology Sept 143(9): 3555–3560, 2002CrossRefGoogle Scholar
  25. 25.
    Carlyle M, Oscar B, Jones JK, John EH: Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension 39(2): 496–501, 2002CrossRefPubMedGoogle Scholar
  26. 26.
    Orbay T, Ercan ZS, Seçkin Z, Göksel M: Pharmacological response of endothelium to microvascular temporary clip application. Surg Neurol 33: 192–194, 1990PubMedCrossRefGoogle Scholar
  27. 27.
    Ercan ZS, Türker RK: Propranolol enhances acetylcholine-induced relaxation in the various arterial segments of rabbit. Arch Int Pharmacodyn Ther 294: 185–193, 1998Google Scholar
  28. 28.
    Altan M, Karasu C, Özüarı A: The effects of type-1 and type-2 diabetes on endothelium-dependent relaxation in rat aorta. Pharm Bioc Behav 33: 519–522, 1989CrossRefGoogle Scholar
  29. 29.
    Vecchione C, Maffei A, Colella S, Aretini A, Poulet R, Frati G, Gentile MT, Fratta L, Trimarco V, Lembo G: Leptin effect on endothelial nitric oxide is mediated through Akt-Endothelial nitric oxide synthase phosphorylation pathway. Diabetes 51(1): 168–173, 2002PubMedCrossRefGoogle Scholar
  30. 30.
    Matsuda K, Teragawa H, Fukuda Y, Nakagawa K, Higashi Y, Chayama K: Leptin causes nitric-oxide independent coronary artery vasodilatation in humans. Hypertens Res 26(2): 147–152, 2003CrossRefPubMedGoogle Scholar
  31. 31.
    Kimura K, Tsuda K, Baba A, Kowabe T, Boh-oka S, Ibata M, Moriwaki C, Hano T, Nishio I: Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. Biochem Biophys Res Commun 273: 745–749, 2000CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Çiğdem Özer
    • 1
  • Şebnem Gülen
    • 2
  • Ergin Dileköz
    • 3
  • Aydan Babül
    • 1
  • Z. Sevim Ercan
    • 3
  1. 1.Department of Physiology, Faculty of MedicineGazi UniversityBeşevler, AnkaraTurkey
  2. 2.Department of Physiology, Faculty of MedicineBaşkent UniversityAnkaraTurkey
  3. 3.Department of Pharmacology, Faculty of MedicineGazi UniversityBeşevler, AnkaraTurkey

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