Skip to main content
Log in

Dehydroepiandrosterone (DHEA) prevents the prostanoid imbalance in mesenteric bed of fructose-induced hypertensive rats

  • ORIGINAL CONTRIBUTION
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Background

In previous studies we reported an altered prostanoid (PR) release-pattern in mesenteric vessels in fructose (F)-overloaded rats, an experimental model of insulin resistance and hypertension. Dehydroepiandrosterone (DHEA) and its precursor Dehydroepiandrosterone sulfate (DHEA-S) are the most abundant circulating steroid hormones produced by the adrenal and recent studies in both cells and animals suggest that DHEA may have acute non-genomic actions that mimic both metabolic and vascular actions of insulin.

Aim of the study

This study was to analyze in F-overloaded rats, the effects of DHEA treatment on arterial blood pressure and the PR production in mesenteric vessels and aorta.

Methods

Male 6 week-old Sprague–Dawley rats were randomly divided in four groups: a control group (C), a DHEA (30 mg/kg/sc/48 h)-treated group (D), a fructose (10% w/v in drinking water)-fed group (F), and both treatments simultaneously group (FD). The systolic blood pressure (SBP) was measured by tail cuff method and glycemia and triglyderidemia were measured by enzymatic assays. The mesenteric beds of all groups were dissected, and incubated in Krebs solution. The PR released were measured by HPLC.

Results

F overload increased SBP and triglyceridemia and decreased the mesenteric vasodilatory PR release. DHEA treatment prevented the increment in SBP and triglyceridemia and decreased vasoconstrictor PR in F-treated rats.

Conclusion

DHEA normalize the PGI2/TX ratio, diminished in F-overloaded rats, through the decrease in thromboxane (TX) production and this could be one of the mechanisms by which DHEA prevented the slight hypertension in F-animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Akarasereenont P, Techatraisak K, Thaworn A, Chotewuttakorn S (2000) The induction of cyclooxygenase-2 by 17-beta-estradiol in endothelial cells is mediated through protein kinase C. Inflamm Res 49:460–465

    Article  CAS  Google Scholar 

  2. Argano M, Parola S, Brignardello E, Manti R, Betteto S, Tamagno E, Danni O, Boccuzzi G (2001) Oxidative stress and eicosanoids in the kidneys of hyperglycemic rats treated with dehydroepiandrosterone. Free Radical Biol Med 31:935–942

    Article  Google Scholar 

  3. Barret-Connor E, Kaw KT, Yen SS (1986) A prospective study of dehydroepiandrosterone sulphate, mortality, and cardiovascular disease. N Engl J Med 315:1519–1524

    Google Scholar 

  4. Baulieu EE, Corpechot C, Dray F, Emiliozzi R, Lebeau MC, Mauvais-Jarvis P, Robel P (1965) An adrenal secreted androgen: dehydroepian- drosterone sulfate. Its metabolism and a tentative generalization on the metabolism of other steroid conjugates in man. Recent Prog Horm Res 21:411–500

    CAS  Google Scholar 

  5. Belanger A, Candas B, Dupont A, Cusan L, Diamond P, Gomez JL, Labrie F (1994) Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. J Clin Endocrinol Metab 79:1086–1090

    Article  CAS  Google Scholar 

  6. Bonnet S, Dumas-de-la-Roque E, Begueret H, Marthan R, Fayon M, Dos Santos P, et al (2003) Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension. PNAS 100:9488–9493

    Article  CAS  Google Scholar 

  7. Chistensen KL, Mulvany MJ (2001) Location of resistance arteries. J Vasc Res 38:1–12

    Article  Google Scholar 

  8. Damiano PF, Cavallero S, Mayer M, Rosón MI, de la Riva I, Fernández B, Puyó AM (2002) Impaired response to insulin associated to protein kinase C in chronic fructose-induced hypertension. Blood Press 11:345–351

    Article  CAS  Google Scholar 

  9. Dhatariya K, Bigelow ML, Nair KS (2005) Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes 54:765–769

    Article  CAS  Google Scholar 

  10. Egan KM, Lawson JA, Fries S, Koller B, Rader DJ, Smyth EM, FritzGerald GA (2004) COX-2-derived prostacyclin confers atheroprotection on female mice. Science 306:1954–1956

    Article  CAS  Google Scholar 

  11. Erdos B, Miller AW, Busija DW (2002) Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin-resistant rats. Am J Physiol 282:H2060–H2065

    CAS  Google Scholar 

  12. Formoso G, Chen H, Kim JA, Montagnani M, Consoli A, Quon MJ (2006) DHEA mimics acute actions of insulin to simulate production of both NO and ET-1 via distinct PI 3-kinase- and MAP-kinase- dependent pathways in vascular endothelium. Mol Endocrinol 20:1153–1163

    Article  CAS  Google Scholar 

  13. Galipeau D, Arikawa E, Sokivov J, McNeill SH (2001) Chronic thromboxane synthase inhibition prevents fructose-fed hypertension. Hypertension 38:872–876

    CAS  Google Scholar 

  14. Hansen PA, Han DH, Nolte LA, Chen M, Holloszy JO (1997) DHEA protects against visceral obesity and muscle insulin resistance in rats fed a high-fat diet. Am J Physiol 273:R1704–R1708

    CAS  Google Scholar 

  15. Harati M, Ani M (2004) Vanadyl sulfate ameliorates insulin resistance and restores plasma dehydroepiandrosterone-sulfate levels in fructose-fed, insulin-resistant rats. Clin Biochem 37:694–697

    Article  CAS  Google Scholar 

  16. Holman RT, Johnson SB, Gerrard JM, Mauer SM, Kupcho-Sandberg S, Brown DM (1983) Arachidonic acid deficiency in streptozotocin-induced diabetes. Proc Natl Acad Sci USA 80:2375–2379

    Article  CAS  Google Scholar 

  17. Hwang JS, Ho H, Hoffman BB, Reaven GM (1987) Fructose induced insulin resistance and hypetension in rats. Hypertension 10:512–516

    CAS  Google Scholar 

  18. Iamberts SW, van den Beld AW, van der Lely AJ (1997) The endocrinology of aging. Science 278:419–424

    Article  Google Scholar 

  19. Jesse RL, Loesser K, Eich DM, Qian YZ, Nestler JE (1995) Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann NY Acad Sci 774:281–290

    Article  CAS  Google Scholar 

  20. Johannes CB, Stellato RK, Feldman HA, Longcope C, McKinlay JB (1999) Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts women’s health study. J Clin Epidemiol 52:95–103

    Article  CAS  Google Scholar 

  21. Karbowska J, Kochan Z (2005) Effect of DHEA on endocrine functions of adipose tissue, the involvement of PPARγ. Biochem Pharm 70:249–257

    Article  CAS  Google Scholar 

  22. Liu D, Dillon JS (2002) Dehydroepiandrosterone activates endothelial cell nitric oxide synthase by a specific plasma membrane receptor coupled to Gαi2,3. J Biol Chem 277:21379–21388

    Article  CAS  Google Scholar 

  23. Mastrocola R, Argano M, Betteto S, Brignardello E, Catalano MG, Danni O, Boccuzzi G (2003) Pro-oxidant effect of dehydroepiadrosterone in rats is mediated by PPAR activation. Life Sci 73:289–299

    Article  CAS  Google Scholar 

  24. Matsuda M, DeFronzo R (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing. Diab Care 22:1462–1470

    Article  CAS  Google Scholar 

  25. Matsumoto T, Kakami M, Noguchi E, Kobayashi T, Kamata K (2007) Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLEFT rats, a model of type 2 diabetes. Am J Physiol Heart Circ Physiol 293:41480–41490

    Article  CAS  Google Scholar 

  26. Mayer MA, Höcht C, Opezzo JA, Taira CA, Fernández BE, Puyó AM (2007) High fructose diet increases anterior hypothalamic alpha 2-adrenoceptors responsiveness. Neurosci Lett 423:128–132

    Article  CAS  Google Scholar 

  27. Miatello R, Risler N, Gonzalez S, Castro C, Ruttler M, Cruzado M (2002) Effects of enalapril on the vascular wall in an experimental model of syndrome X. Am J Hypertens 15:872–878

    Article  CAS  Google Scholar 

  28. Mohan PF, Ihnen JS, Levin BE, Cleary MP (1990) Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity. J Nutr 120:1103–1114

    CAS  Google Scholar 

  29. Montagnani M, Chen H, Barr VA, Quon MJ (2001) Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem 276:30392–303928

    Article  CAS  Google Scholar 

  30. Muniyappa R, Montagnani M, Koh KK, Quon MJ (2007) Cardiovascular actions of insulin. Endocr Rev 28:463–491

    Article  CAS  Google Scholar 

  31. Nagal Y, Nishio Y, Nakamura T, Maegawa H, Kikkawa R, Kasiwagi A (2002) Amelioration of high fructose-induced metabolic derangements by activation of PPARα. Am J Physiol 282:E1180–E1190

    Google Scholar 

  32. Nestler JE, Clore JN, Blackard WG (1991) Metabolism and actions of dehydroepiandrosterone in humans. J Steroid Biochem Mol Biol 40:599–605

    Article  CAS  Google Scholar 

  33. Nestler JE, Usiskin KS, Barlascini CO, Welty DF, Clore JN, Blackard WG (1989) Suppression of serum dehydroepiandrosterone sulfate levels by insulin: an evaluation of possible mechanisms. J Clin Endocrinol Metab 69:1040–1046

    Article  CAS  Google Scholar 

  34. Peredo HA (2001) Prostanoid release, constrictor responses to noradrenaline in the mesenteric vascular bed in non-insulin-dependent diabetes mellitus. J Auton Pharmacol 21:131–137

    Article  CAS  Google Scholar 

  35. Peredo HA, Mayer MA, Carranza A, Puyó AM (2008) Pioglitazone and losartan prevent hypertension and hypertrigliceridemia and modify vascular prostanoids in fructosa-overloaded rats. Clin Exp Hypertens (in press)

  36. Peredo HA, Mayer MA, Rodríguez-Fermepín M, Grinspon D, Puyó AM (2006) Oral treatment and in vitro incubation with fructose modify vascular prostanoid production in the rat. Auton Autacoid Pharmacol 26:15–20

    Article  CAS  Google Scholar 

  37. Puyo AM, Mayer MA, Cavallero S, Donoso AS, Peredo HA (2008) Fructose overload modifies vascular morphology and prostaglandin production in rats. Clin Exp Hypertens 30:159–169

    Article  CAS  Google Scholar 

  38. Pérez de Heredia F, Cerezo D, Zamora S, Garaulet M (2007) Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats. Br J Nutr 97:464–470

    Article  CAS  Google Scholar 

  39. Reaven GM (1988) Banting lecture 1988: role of insulin resistance in human disease. Diabetes 37:1507–1597

    Google Scholar 

  40. Reaven GM, Ho H (1991) Sugar-induced hypertension in Sprague–Dawley rats. Am J Hypertens 4:610–614

    CAS  Google Scholar 

  41. Rettori V, Gimeno M, Lyson K, McCaan S (1992) Nitric oxide mediates norepinephrine-induced prostaglandin E2 release from the hypothalamus. Proc Natl Acad Sci USA 89:11543–11546

    Article  CAS  Google Scholar 

  42. Segal MS, Gollub E, Johnson RJ (2007) Is the fructose index more relevant with regards to cardiovascular disease than the glycemic index? Eur J Nutr 46(7):406–417

    Article  CAS  Google Scholar 

  43. Setty B, Stuart M (1986) 15-Hydrixy-5,8,11,13-eicosatetraenoic acids inhibits human vascular cyclooxygenase, potential role in diabetic vascular disease. J Clin Invest 77:202–211

    Article  CAS  Google Scholar 

  44. Shafagoj Y, Opoku J, Qureshi D, Regelson W, Kalimi M (1992) Dehydroepiandrosterone prevents dexamethasone-induced hypertension in rats. Am J Physiol 263:E210–E213

    CAS  Google Scholar 

  45. Simoncini T, Hafezi-Mogham A, Brazil DP, Ley K, Chin WW, Liao JK (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-kinase . Nature 407:538–541

    Article  CAS  Google Scholar 

  46. Thornburn W, Storlien LH, Jendius AB, Khouri S (1989) Fructose-induced insulin resistance and elevated plasma triglycerides in rats. Am J Clin Nutr 49:1155–1163

    Google Scholar 

  47. Verma S, Bhanot S, Yao J, McNeill JH (1996) Defective endothelium-dependent relaxation in fructose-hypertensive rats. Am J Hypertens 9:370–376

    Article  CAS  Google Scholar 

  48. Xi L, Qian Z, Xu G, Zheng S, Sun S, Wen N, Sheng L, Shi Y, Zhang Y (2007) Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. J Nutr Biochem 18:64–72

    Article  CAS  Google Scholar 

  49. Yamaguchi Y, Tanaka S, Yamakawa T, Yamakawa T, Kimura M, Ukawa K et al (1988) Reduced serum dehydroepiandrosterone levels in diabetic patients with hyperinsulinaemia. Clin Endocrinol (Oxf) 49:377–383

    Article  Google Scholar 

  50. Yorek JA, Coppey LJ, Gellett JS, Davidson EP, King X, Lund DD, Dillon JS (2002): Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function. Am J Physiol Endocrinol Metab 283:E1067–E1075

    CAS  Google Scholar 

  51. Yoshimata T, Yoneyama A, Jin-no Y, Tamai N, Kamiya Y (1999) Effects of dehydroepiandroseterone on mitogen-activated protein kinase in human aortic smooth muscle cells. Life Sci 65:431–440

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was suppored by grants from the Secretaría de Ciencia y Técnica of the Universidad de Buenos Aires (Code B 109) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), PIP 2109/00 and PIP 5497. We gratefully acknowledge the valuable assistance of Dr. Belisario Fernandez in discussing and revising the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrea Carranza.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peredo, H.A., Mayer, M., Faya, I.R. et al. Dehydroepiandrosterone (DHEA) prevents the prostanoid imbalance in mesenteric bed of fructose-induced hypertensive rats. Eur J Nutr 47, 349–356 (2008). https://doi.org/10.1007/s00394-008-0734-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-008-0734-7

Keywords

Navigation