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Early Functional Changes in Rat Arteries and Microcirculatory Vessels while Modeling Metabolic Syndrome

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Abstract

Early changes in the cardiovascular system of young Wistar rats were studied in modeling metabolic syndrome by a fructose load. It was found that despite some weight loss in rats fed a fructose diet, as compared to control animals, these animals showed the signs of metabolic syndrome: hyperglycemia, insulin resistance, dyslipidemia, increased activity of the sympathetic nervous system, arterial hypertension. Changes in the mesenteric arteries included an increase in the reactivity to phenylephrine and a decrease in acetylcholine-induced dilation due to decreased NO production by the endothelium, which is to a certain extent compensated by an increased production of the endothelium-derived hyperpolarizing factor realizing its effects through the activation of intermediate-conductance Ca2+-activated K+-channels. Fructose load led to the inhibition of soluble guanylate cyclase in arterial smooth muscle cells. In the skin microcirculatory bed of fructose-loaded rats, perfusion remained at the level typical for control animals, while skin microvessels showed an increase in neurogenic tone and an attenuation of endothelium-dependent tone. A decreased endothelial NO production was found in microcirculatory vessels, which was compensated by the synthesis of other endothelium-derived vasodilating factors.

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REFERENCES

  1. Saklayen MG (2018) The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep 20 (2): 12. https://doi.org/10.1007/s11906-018-0812-z

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rotar OP, Libis RA, Isaeva EN, Erina AM, Shavshin DA, Moguchaya EV, Kolesova EP, Boyarinova MA, Moroshkina NV, Yakovleva OI, Solntsev VN, Konradi AO, Shlyakhto EV (2012) Metabolic syndrome prevalence in russian cities. Russ J Cardiol 2: 55–62. (In Russ).

    Google Scholar 

  3. Lopez-Candales A, Hernández Burgos PM, Hernandez-Suarez DF, Harris D (2017) Linking Chronic Inflammation with Cardiovascular Disease: From Normal Aging to the Metabolic Syndrome. J Nat Sci 3(4): e341.

    PubMed  PubMed Central  Google Scholar 

  4. Bovolini A, Garcia J, Andrade MA, Duarte JA (2021) Metabolic Syndrome Pathophysiology and Predisposing Factors. Int J Sports Med 42(3): 199–214. https://doi.org/10.1055/a-1263-0898

    Article  PubMed  Google Scholar 

  5. Lee AM, Gurka MJ, DeBoer MD (2016) Trends in Metabolic Syndrome Severity and Lifestyle Factors Among Adolescents. Pediatrics 137(3): e20153177. https://doi.org/10.1542/peds.2015-3177

    Article  PubMed  PubMed Central  Google Scholar 

  6. DeBoer MD (2019) Assessing and Managing the Metabolic Syndrome in Children and Adolescents. Nutrients 11(8): 1788. https://doi.org/10.3390/nu11081788

    Article  CAS  PubMed Central  Google Scholar 

  7. Samson SL, Garber AJ (2018) Metabolic syndrome. Endocrinol Metab Clin North Am 43(1): 1–23. https://doi.org/10.1016/j.ecl.2013.09.009

    Article  Google Scholar 

  8. Fuchs T, Loureiro MP, Macedo LE, Nocca D, Nedelcu M, Costa-Casagrande TA (2018) Animal models in metabolic syndrome. Rev Col Bras Circ 45(5): e1975. https://doi.org/10.1590/0100-6991e-20181975

    Article  Google Scholar 

  9. Nilsson C, Raun K, Yan FF, Larsen MO, Tang-Christensen M (2012) Laboratory animals as surrogate models of human obesity. Acta Pharmacol Sin 33(2): 173–181. https://doi.org/10.1038/aps.2011.203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Estadella D, Oyama LM, Dâmaso AR, Ribeiro EB, Oller Do Nascimento CM (2004) Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats. Nutrition 20(2): 218–224. https://doi.org/10.1016/j.nut.2003.10.008

    Article  CAS  PubMed  Google Scholar 

  11. Wong SK, Chin KY, Suhaimi FH, Fairus A, Ima-Nirwana S (2016) Animal models of metabolic syndrome: a review. Nutr Metab (Lond)13: 65. https://doi.org/10.1186/s12986-016-0123-9

  12. Sato Mito N, Suzui M, Yoshino H, Kaburagi T, Sato K (2009) Long term effects of high fat and sucrose diets on obesity and lymphocyte proliferation in mice. J Nutr Health Aging 13(7): 602–606. https://doi.org/10.1007/s12603-009-0170-2

    Article  CAS  PubMed  Google Scholar 

  13. Aydin S, Aksoy A, Aydin S, Kalayci M, Yilmaz M, Kuloglu T, Citil C, Catak Z (2014) Today’s and yesterday’s of pathophysiology: biochemistry of metabolic syndrome and animal models. Nutrition 30(1): 1–9. https://doi.org/10.1016/j.nut.2013.05.013

    Article  CAS  PubMed  Google Scholar 

  14. Basciano H, Federico L, Adeli K (2005) Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2(1): 5. https://doi.org/10.1186/1743-7075-2-5

  15. Johnson RJ, Segal MS, Sautin Y, Nakagawa T, Feig DI, Kang DH, Gersch MS, Benner S, Sánchez-Lozada LG (2007) Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 86(4): 899–906. https://doi.org/10.1093/ajcn/86.4.899

    Article  CAS  PubMed  Google Scholar 

  16. Sánchez-Lozada LG, Tapia E, Jiménez A, Bautista P, Cristóbal M, Nepomuceno T, Soto V, Avila-Casado C, Nakagawa T, Johnson RJ, Herrera-Acosta J, Franco M (2007) Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am J Physiol Renal Physiol 292(1): F423–F429. https://doi.org/10.1152/ajprenal.00124.2006

    Article  CAS  PubMed  Google Scholar 

  17. Kotsis V, Jordan J, Micic D, Finer N, Leitner DR, Toplak H, Tokgozoglu L, Athyros V, Elisaf M, Filippatos TD, Redon J, Redon P, Antza C, Tsioufis K, Grassi G, Seravalle G, Coca A, Sierra C, Lurbe E, Stabouli S, Jelakovic B, Nilsson PM (2018) Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part A: mechanisms of obesity induced hypertension, diabetes and dyslipidemia and practice guidelines for treatment. J Hypertens 36(7): 1427–1440. https://doi.org/10.1097/HJH.0000000000001730

    Article  CAS  PubMed  Google Scholar 

  18. Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP (2010) Endothelial dysfunction in metabolic syndrome: prevalence, pathogenesis and management. Nutr Metab Cardiovasc Dis 20(2): 140–146. https://doi.org/10.1016/j.numecd.2009.08.006

    Article  CAS  PubMed  Google Scholar 

  19. Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115(10): 1285–1295. https://doi.org/10.1161/CIRCULATIONAHA.106.652859

    Article  PubMed  Google Scholar 

  20. Krupatkin AI, Sidorov VV (2005) Laser Doppler flowmetry of blood microcirculation. Medicine, M. (In Russ).

    Google Scholar 

  21. Serbis A, Giapros V, Galli-Tsinopoulou A, Siomou E (2020) Metabolic Syndrome in Children and Adolescents: Is There a Universally Accepted Definition? Does it Matter? Metab Syndr Relat Disord 18(10): 462–470. https://doi.org/10.1089/met.2020.0076

    Article  CAS  PubMed  Google Scholar 

  22. Rohman M, Lukitasari M, Nugroho D, Nashi W, Nugraheini N, Sardjono T (2017) Development of an Experimental Model of Metabolic Syndrome in Sprague Dawley Rat. Res J Life Sci 4(1): 76–86. https://doi.org/10.21776/ub.rjls.2017.004.01.10

    Article  Google Scholar 

  23. Moreno-Fernández S, Garcés-Rimón M, Vera G, Astier J, Landrier JF, Miguel M (2018) High Fat/High Glucose Diet Induces Metabolic Syndrome in an Experimental Rat Model. Nutrients 10(10): 1502. https://doi.org/10.3390/nu10101502

    Article  CAS  PubMed Central  Google Scholar 

  24. Sheludiakova A, Rooney K, Boakes RA (2012) Metabolic and behavioural effects of sucrose and fructose/glucose drinks in the rat. Eur J Nutr 51(4): 445–454. https://doi.org/10.1007/s00394-011-0228-x

    Article  CAS  PubMed  Google Scholar 

  25. Bertram CE, Hanson MA (2001) Animal models and programming of the metabolic syndrome. Br Med Bull 60: 103–121. https://doi.org/10.1093/bmb/60.1.103

    Article  CAS  PubMed  Google Scholar 

  26. Oron-Herman M, Kamari Y, Grossman E, Yeger G, Peleg E, Shabtay Z, Shamiss A, Sharabi Y (2008) Metabolic syndrome: comparison of the two commonly used animal models. Am J Hypertens 21(9): 1018–1022. https://doi.org/10.1038/ajh.2008.218

    Article  CAS  PubMed  Google Scholar 

  27. Litwin M, Kułaga Z (2021) Obesity, metabolic syndrome, and primary hypertension. Pediatr Nephrol 36(4): 825–837. https://doi.org/10.1007/s00467-020-04579-3

    Article  PubMed  Google Scholar 

  28. da Silva AA, do Carmo JM, Li X, Wang Z, Mouton AJ, Hall JE (2020) Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited. Can J Cardiol 36(5): 671–682. https://doi.org/10.1016/j.cjca.2020.02.066

    Article  PubMed  Google Scholar 

  29. Hert KA, Fisk PS 2nd, Rhee YS, Brunt AR (2014) Decreased consumption of sugar-sweetened beverages improved selected biomarkers of chronic disease risk among US adults: 1999 to 2010. Nutr Res 34(1): 58–65. https://doi.org/10.1016/j.nutres.2013.10.005

    Article  CAS  PubMed  Google Scholar 

  30. Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP (2010) Endothelial dysfunction in metabolic syndrome: prevalence, pathogenesis and management. Nutr Metab Cardiovasc Dis 20(2): 140–146. https://doi.org/10.1016/j.numecd.2009.08.006

    Article  CAS  PubMed  Google Scholar 

  31. Spieker LE, Noll G, Ruschitzka FT, Maier W, Lüscher TF (2000) Working under pressure: the vascular endothelium in arterial hypertension. J Hum Hypertens 14(10–11): 617–630. https://doi.org/10.1038/sj.jhh.1001012

    Article  CAS  PubMed  Google Scholar 

  32. Clements ML, Banes AJ, Faber JE (1997) Effect of mechanical loading on vascular alpha 1D- and alpha 1B-adrenergic receptor expression. Hypertension 29(5): 1156–1164. https://doi.org/10.1161/01.hyp.29.5.1156

    Article  CAS  PubMed  Google Scholar 

  33. Félétou M, Köhler R, Vanhoutte PM (2012) Nitric oxide: orchestrator of endothelium-dependent responses. Ann Med 44(7): 694–716. https://doi.org/10.3109/07853890.2011.585658

    Article  CAS  PubMed  Google Scholar 

  34. Li JC, Velagic A, Qin CX, Li M, Leo CH, Kemp-Harper BK, Ritchie RH, Woodman OL (2021) Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries. Front Pharmacol 21(11): 585740. https://doi.org/10.3389/fphar.2020.585740

    Article  CAS  Google Scholar 

  35. Yada T, Shimokawa H, Tachibana H (2018) Endothelium-dependent hyperpolarization-mediated vasodilatation compensates nitric oxide-mediated endothelial dysfunction during ischemia in diabetes-induced canine coronary collateral microcirculation in vivo. Microcirculation 25(5): e12456. https://doi.org/10.1111/micc.12456

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the program entitled “Basic Scientific Research for the Long-Term Development and Competitiveness of the Society and State” (47_110_LTDaC, 64.1)

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Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia

    I. A. Tsareva, G. T. Ivanova & G. I. Lobov

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  1. I. A. Tsareva
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  2. G. T. Ivanova
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  3. G. I. Lobov
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Conceptualization and experimental design, editing of the manuscript (G.I.L.); literature review, data collection and analysis, writing of the manuscript (I.A.Ts., G.T.I.).

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Correspondence to I. A. Tsareva.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 9, pp. 1134–1147https://doi.org/10.31857/S0869813922090084.

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Tsareva, I.A., Ivanova, G.T. & Lobov, G.I. Early Functional Changes in Rat Arteries and Microcirculatory Vessels while Modeling Metabolic Syndrome. J Evol Biochem Phys 58, 1471–1481 (2022). https://doi.org/10.1134/S0022093022050179

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