Journal of Physiology and Biochemistry

, Volume 70, Issue 1, pp 81–91

Vascular damage in obese female rats with hypoestrogenism

  • Luis Angel Lima-Mendoza
  • Juventino Colado-VelázquezIII
  • Patrick Mailloux-Salinas
  • Josué V. Espinosa-Juárez
  • Norma L. Gómez-Viquez
  • Tzindilu Molina-Muñoz
  • Fengyang Huang
  • Guadalupe Bravo
Original Paper

Abstract

Increase in body weight and adiposity has deleterious consequences on health. The aim of this study was to compare morphological and metabolic changes in the arterial vessels of Wistar rats with conditions of obesity, hypoestrogenism, and hypoestrogenism plus obesity. Ovariectomized rats (hypoestrogenic condition) received 30 % sugar in drinking water plus standard diet during 10 weeks. The hypoestrogenic-obese (HE-OB) group presented increase in weight, blood pressure, hypertriglyceridemia, and hyperglycemia compared with other groups. The morphological study in aortic vessels from HE showed damage in endothelial smooth muscle tissue compared with the other groups. Adipose cells volume in HE-OB (59.33 ± 2.38 μ3 × 105) and obese (OB) (54.95 ± 1.36 μ3 × 105) groups were significantly larger than control group (36.38 ± 0.98 μ3 × 105). In the HE group adipocyte hyperplasia was observed, while in OB group adipocyte hypertrophy and hyperplasia was shown. The vascular reactivity in HE-OB and OB groups presented decrease in the relaxation to acetylcholine compared with control conditions (p < 0.05), whereas the addition of NG-nitro-l-arginine methyl ester resulted in a greater inhibition of relaxation in HE-OB and OB groups compared with control conditions (p < 0.05). These findings suggest that the dysfunction in blood vessels observed in estrogen deficiency and obesity conditions contributes to early cardiovascular alterations.

Keywords

Hypoestrogenism Obesity Rats Vascular dysfunction 

References

  1. 1.
    Arjmandi BH, Alekel L, Hollis BW, Amin D, Stacewics-Sapuntzakis M et al (1996) Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 126:161–167PubMedGoogle Scholar
  2. 2.
    Barton M (2010) Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis. Pflügers Arch 460:825–837PubMedCrossRefGoogle Scholar
  3. 3.
    Barton M (2013) Prevention and endothelial therapy of coronary artery disease. Curr Opin Pharmacol 13(2):226–241PubMedCrossRefGoogle Scholar
  4. 4.
    Beatty W, O'Briant D, Vilberg T (1975) Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions. Pharmac Biochem Behav 3:539–544CrossRefGoogle Scholar
  5. 5.
    Berger JJ, Barnard RJ (1999) Effect of diet on fat cell size and hormone-sensitive lipase activity. J App Physiol 87:227–232Google Scholar
  6. 6.
    Boqué N, Campión J, Paternain L, García-Díaz DF, Galarraga M et al (2009) Influence of dietary macronutrient composition on adiposity and cellularity of different fat depots in Wistar rats. J Physiol Biochem 65:387–395PubMedCrossRefGoogle Scholar
  7. 7.
    Brownlee M (2003) Radical explanation for glucose-induced β-cell dysfunction. J Clin Invest 112:1788–1790PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Carillon J, Romain C, Bardy G, Fouret G, Feillet-Coudray C et al (2013) Cafeteria diet induces obesity and insulin resistance associated with oxidative stress but not with inflammation. Improvement by dietary supplementation of a melon superoxide dismutase. Free Radic Biol Med 65:254–261PubMedCrossRefGoogle Scholar
  9. 9.
    Commerford SR, Pagliassotti MJ, Melby CL, Wei Y, Gayles EC, Hill JO (2000) Fat oxidation, lipolysis, and free fatty acid cycling in obesity-prone and obesity-resistant rats. Am J Physiol Endocrino Metab 279:E875–E885Google Scholar
  10. 10.
    De Ferranti S, Mozaffarian D (2008) The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem 54:945–955PubMedCrossRefGoogle Scholar
  11. 11.
    Diamond F (2002) The endocrine function of adipose tissue. Growth Genet Horm 18:17–22Google Scholar
  12. 12.
    Dobrian AD, Davies MJ, Prewitt RL, Lauterio TJ (2000) Development of hypertension in a rat model of diet-induced obesity. Hypertension 35:1009–1015PubMedCrossRefGoogle Scholar
  13. 13.
    Dobrian AD, Davies MJ, Schriver SD, Lauterio TJ, Prewitt RL (2001) Oxidative stress in a rat model of obesity-induced hypertension. Hypertension 37(2 Pt 2):554–560PubMedCrossRefGoogle Scholar
  14. 14.
    Dubrovska G, Verlohren S, Luft FC, Gollasch M (2004) Mechanisms of ADRF release from rat aortic adventitial adipose tissue. Am Physiol Heart Circ Physiol 286:H1107–H1113CrossRefGoogle Scholar
  15. 15.
    Duckles SP, Krause DN, Stirone C, Procaccio V (2006) Estrogen and mitochondria: a new paradigm for vascular protection? Mol Interv 6:26–35PubMedCrossRefGoogle Scholar
  16. 16.
    Faust IM, Johnson PR, Stern JS, Hirsch J (1978) Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physio 235:E279–E286Google Scholar
  17. 17.
    Flegal KM, Carroll MD, Ogden CL, Johnson CL (2002) Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288:1723–1727PubMedCrossRefGoogle Scholar
  18. 18.
    Granger DN, Rodrigues SF, Yildirim A, Senchenkova EY (2010) Microvascular responses to cardiovascular risk factors. Microcirculation 17(3):192–205PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Hausman DB, Fine JB, Tagra K, Fleming SS, Martin RJ, DiGirolamo M (2003) Regional fat pad growth and cellularity in obese Zucker rats: modulation by caloric restriction. Obes Res 11:674–682PubMedCrossRefGoogle Scholar
  20. 20.
    Hill-Pryor C, Dunbar JC (2006) The effect of high fat-induced obesity on cardiovascular and physical activity and opioid responsiveness in conscious rats. Clin Exp Hypertens 28:13–14CrossRefGoogle Scholar
  21. 21.
    Kanarek RB, Orthen-Gambill N (1982) Differential effects of sucrose, fructose and glucose on carbohydrate-induced obesity in rats. J Nutr 112:1546–1554PubMedGoogle Scholar
  22. 22.
    Kang LS, Chen B, Reyes RA, Leblanc AJ, Teng B et al (2011) Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles. Am J Physiol Heart Circ Physiol 300(6):H2105–H2115PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Kannel WB, Brand N, Skinner JJ Jr, Dawber TR, McNamara PM (1967) The relation of adiposity to blood pressure and development of hypertension. The Framingham study. Ann Intern Med 67:48–59PubMedCrossRefGoogle Scholar
  24. 24.
    Kershaw E, Flier S (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556PubMedCrossRefGoogle Scholar
  25. 25.
    Lemonnier D (1972) Effect of age, sex, and sites on the cellularity of the adipose tissue in mice and rats rendered obese by a high-fat diet. J Clin Invest 51:2907–2915PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Liang Y, Akishita M, Kim S et al (2002) Estrogen receptor beta is involved in the anorectic action of estrogen. Int J Obes 26:1103–1109CrossRefGoogle Scholar
  27. 27.
    Löhn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM (2002) Periadventitial fat releases a vascular relaxing factor. FASEB 16:1057–1063CrossRefGoogle Scholar
  28. 28.
    MacMahon S, Peto R, Cutler J, Collins R, Sorlie P et al (1990) Blood pressure, stroke, and coronary heart disease. Part I, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335:765–774PubMedCrossRefGoogle Scholar
  29. 29.
    Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide: Biol Chem 5(1):62–71CrossRefGoogle Scholar
  30. 30.
    Misso ML, Murata Y, Boon WC, Jones ME, Britt KL et al (2003) Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse. Endocrinology 144:1474–1480PubMedCrossRefGoogle Scholar
  31. 31.
    Newbold RR, Padilla-Banks E, Jefferson WN, Heindel JJ (2008) Effects of endocrine disruptors on obesity. Int J Androl 31:201–208PubMedCrossRefGoogle Scholar
  32. 32.
    Novella S, Dantas AP, Segarra G, Novensà L, Bueno C et al (2010) Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice. Exp Gerontol 45(11):868–874PubMedCrossRefGoogle Scholar
  33. 33.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRefGoogle Scholar
  34. 34.
    Piya MK, McTernan PG, Kumar S (2013) Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J Endocrinol 216(1):T1–T15PubMedCrossRefGoogle Scholar
  35. 35.
    Prophet EB, Mills B, Arrington JB (1992) Laboratory methods in histotechnology. American Registry of Pathology, WashingtonGoogle Scholar
  36. 36.
    Rappelli A (2002) Hypertension and obesity after the menopause. J Hyperten 20:S26–S28Google Scholar
  37. 37.
    Roberts CK, Barnard RJ, Sindhu RK, Jurczak M, Ehdaie A et al (2005) A high fat, refined-carbohydrate diet induces endothelial dysfunction and oxidant/antioxidant imbalance and depresses NOS protein expression. J Appl Physiol 98:203–210PubMedCrossRefGoogle Scholar
  38. 38.
    Roberts CK, Vaziri ND, Barnard RJ (2001) Protective effect of estrogen on gender-specific development of diet-induced hypertension. J Appl Physiol 91:2005–2009PubMedGoogle Scholar
  39. 39.
    Romero-Silva S, Martínez MA, Romero-Romero LP, Rodriguez O, Salas G et al (2011) Effects of honey against the accumulation of adipose tissue and the increased blood pressure on carbohydrate-induced obesity in rat. Lett Drug Des Discov 8:69–75CrossRefGoogle Scholar
  40. 40.
    Roy EJ, Wade GN (1977) Role of food intake in estradiol-induced body weight changes in female rats. Horm Behav 8:265–274PubMedCrossRefGoogle Scholar
  41. 41.
    Sorensen MB, Collins P, Ong PJ, Webb CM, Hayward CS et al (2002) Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance. Circulation 106(13):1646–1651PubMedCrossRefGoogle Scholar
  42. 42.
    Svendsen O, Hassager C, Christiansen C (1995) Age and menopause associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry. Metabolism 44:369–373PubMedCrossRefGoogle Scholar
  43. 43.
    Tappy L, Le KA (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90:23–46PubMedCrossRefGoogle Scholar
  44. 44.
    Tchernof A, Poehlman ET, Despres JP (2000) Body fat distribution, the menopause transition, and hormone replacement therapy. Diabetes Metab 26:12–20PubMedGoogle Scholar
  45. 45.
    Triggle CR, Hollenberg M, Anderson TJ, Ding H, Jiang Y et al (2003) The endothelium in health and disease–a target for therapeutic intervention. J Smooth Muscle Res 39:249–267PubMedCrossRefGoogle Scholar
  46. 46.
    Young J, Landsberg L (1981) Effect of oral glucose on blood pressure in the spontaneously hypertensive rat. Metabolism 30:421–424PubMedCrossRefGoogle Scholar
  47. 47.
    Zhang L, Fujii S, Kosaka H (2007) Effect of oestrogen on reactive oxygen species production in the aortas of ovariectomized Dahl salt-sensitive rats. J Hypertens 25(2):407–414PubMedCrossRefGoogle Scholar

Copyright information

© University of Navarra 2013

Authors and Affiliations

  • Luis Angel Lima-Mendoza
    • 1
  • Juventino Colado-VelázquezIII
    • 1
  • Patrick Mailloux-Salinas
    • 1
  • Josué V. Espinosa-Juárez
    • 1
  • Norma L. Gómez-Viquez
    • 1
  • Tzindilu Molina-Muñoz
    • 1
  • Fengyang Huang
    • 2
  • Guadalupe Bravo
    • 1
    • 3
  1. 1.Pharmacobiology DepartmentCinvestav-IPNMexicoMexico
  2. 2.Department of Pharmacology and ToxicologyHospital Infantil de México Federico GómezMexicoMexico
  3. 3.Departamento Farmacobiología, Cinvestav-IPNMexicoMexico

Personalised recommendations