Mesenteric Artery Reactivity in the Development of Metabolic Syndrome in Rats Fed on a High-Fat Diet

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Higt fat diet can lead to the development of metabolic syndrome (MS). However, the question of the mechanisms of pathophysiological processes in MS has not been studied enough. The aim of the work was to study the effect of a high-fat diet (HFD) on the reactivity of the mesenteric arteries of Wistar rats in vivo, as well as to evaluate the change in the mechanisms of endothelium-dependent arterial dilatation in HFD. The HFD-group of rats (n = 25) received HFD containing 50% animal fat for 10 weeks, the control group (n = 25) received a standard diet. The effect of HFD on endothelium-dependent and endothelium-independent responses of the mesenteric arteries under the action of agonists in the absence and with the use of blockers of NO-synthase (L-NAME), cyclooxygenase (indomethacin), and K+-channels (tetraethylammonium) was assessed using photomicrography and video recording of mesenteric artery diameter in vivo. HFD in rats led to the development of MS, including dyslipidemia, hyperglycemia and insulin resistance, and an increase in blood pressure. MS was accompanied by impaired functional state of the mesenteric arteries. In rats of the HFD group, compared with the control group, there was an increase in the constrictor reaction to phenylephrine by 29%, as well as a decrease in the reactivity of vessels previously contracted by phenylephrine under the action of acetylcholine by 36%. Pre-incubation of vessels with blockers reduced the amplitude of relaxation under the action of acetylcholine, compared with the initial acetylcholine-induced vasorelaxation, in HFD-group rats: with L-NAME – by 47%, L-NAME and indomethacin – by 50%, L-NAME, indomethacin and tetraethylammonium – by 65%; in the control group – by 69, 72 and 83%, respectively. HFD had no significant effect on the amplitude of vasodilation under the action of sodium nitroprusside. Thus, endothelial dysfunction in HFD-treated rats was mediated both by impairment of NO-dependent mechanisms of vasodilation, in particular, by a decrease in NO production by the endothelium, and by a decrease in the effectiveness of ВКСа. The decrease in NO bioavailability in HFD was partially compensated by the activation of endothelial hyperpolarization mechanisms (mediated by IKCa and SKCa activities) in acetylcholine-induced vasodilation.

About the authors

G. T. Ivanova

Pavlov Institute of Physiology, Russian Academy of Scienes

Author for correspondence.
Email: ivanovagt@infran.ru
Russia, St. Petersburg

References

  1. 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
  2. Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL (2017) Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis 11(8): 215–225. https://doi.org/10.1177/1753944717711379
  3. Wong SK, Chin KY, Suhaimi FH, Fairus A, Ima-Nirwana S (2016) Animal models of metabolic syndrome: a review. Nutr Metab 13: 65. https://doi.org/10.1186/s12986-016-0123-9
  4. Abdulrahman AO, Kuerban A, Alshehri ZA, Abdulaal WH, Khan JA, Khan MI (2020) Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet. Diabetes Metab Syndr Obes 13: 3337–3348. https://doi.org/10.2147/DMSO.S268146
  5. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruhart JC, James WPT, Loria CM, Smith SC Jr (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120: 1640–1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644
  6. Koliaki C, Liatis S, Kokkinos A (2019) Obesity and Cardiovascular Disease: Revisiting an Old Relationship. Metabolism 92: 98–107. https://doi.org/10.1016/j.metabol.2018.10.011
  7. Stanek A, Fazeli B, Bartuś S, Sutkowska E (2018) The Role of Endothelium in Physiological and Pathological States: New Data. Biomed Res Int 2018: e1098039. https://doi.org/10.1155/2018/1098039
  8. Suzuki T, Hirata K, Elkind MS, Jin Z, Rundek T, Miyake Y, Boden-Albala B, Di Tullio MR, Sacco R, Homma S (2008) Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAS). Am Heart J 156(2): 405–410. https://doi.org/10.1016/j.ahj.2008.02.022
  9. Dow CA, Stauffer BL, Greiner JJ, DeSouza CA (2015) Influence of habitual high dietary fat intake on endothelium-dependent vasodilation. Appl Physiol Nutr Metab 40(7): 711–715. https://doi.org/10.1139/apnm-2015-0006
  10. Lozano-Cuenca J, Valencia-Hernández I, López-Canales OA, Flores-Herrera H, López-Mayorga RM, Castillo-Henkel EF, López-Canales JS (2020) Possible mechanisms involved in the effect of the subchronic administration of rosuvastatin on endothelial function in rats with metabolic syndrome. Braz J Med Biol Res 53(2): e9304. https://doi.org/10.1590/1414-431X20199304
  11. Oishi JC, Castro CA, Silva KA, Fabricio V, Cárnio EC, Phillips SA, Duarte ACGO, Rodrigues GJ (2018) Endothelial Dysfunction and Inflammation Precedes Elevations in Blood Pressure Induced by a High-Fat Diet. Arq Bras Cardiol 110(6): 558–567. https://doi.org/10.5935/abc.20180086
  12. Oliva L, Aranda T, Caviola G, Fernández-Bernal A, Alemany M, Fernández-López JA, Remesar X (2017) In rats fed high-energy diets, taste, rather than fat content, is the key factor increasing food intake: a comparison of a cafeteria and a lipid-supplemented standard diet. Peer J 5: e3697. https://doi.org/10.7717/peerj.3697
  13. Ramalho L, da Jornada MN, Antunes LC, Hidalgo MP (2017) Metabolic disturbances due to a high-fat diet in a non-insulin-resistant animal model. Nutr Diabetes 7(3): e245. https://doi.org/10.1038/nutd.2016.47
  14. Garcia ML, Milanez MIO, Nishi EE, Sato AYS, Carvalho PM, Nogueira FN, Campos RR, Oyama LM, Bergamaschi CT (2021) Retroperitoneal adipose tissue denervation improves cardiometabolic and autonomic dysfunction in a high fat diet model. Life Sci 283: 119841. https://doi.org/10.1016/j.lfs.2021.119841
  15. Gradel AKJ, Salomonsson M, Sørensen CM, Holstein-Rathlou NH, Jensen LJ (2018) Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels. Clin Sci (Lond) 132(4): 461–474. https://doi.org/10.1042/CS20171408
  16. Skurk T, Alberti-Huber C, Herder C, Hauner H (2007) Relationship between Adipocyte Size and Adipokine Expression and Secretion. J Clin Endocrinol Metab 92: 1023–1033. https://doi.org/10.1210/jc.2006-1055
  17. Sudhakar M, Silambanan S, Chandran AS, Prabhakaran AA, Ramakrishnan R (2018) C-Reactive Protein (CRP) and Leptin Receptor in Obesity: Binding of Monomeric CRP to Leptin Receptor. Front Immunol 9: 1167. https://doi.org/10.3389/fimmu.2018.01167
  18. Mahajan R, Lau DH, Sanders P (2015) Impact of obesity on cardiac metabolism, fibrosis, and function. Trends Cardiovasc Med 25: 119–126. https://doi.org/10.1016/j.tcm.2014.09.005
  19. Gutiérrez-Cuevas J, Sandoval-Rodríguez A, Monroy-Ramírez HC, Mercado MV-D, Santos-García A, Armendáriz-Borunda J (2020) Prolonged-release pirfenidone prevents obesity-induced cardiac steatosis and fibrosis in a mouse NASH model. Cardiovasc Drugs Ther 35(5): 927–938. https://doi.org/10.1007/s10557-020-07014-9
  20. Kwiatkowski G, Bar A, Jasztal A, Chłopicki S (2021) MRI-based in vivo detection of coronary microvascular dysfunction before alterations in cardiac function induced by short-term high-fat diet in mice. Sci Rep 11(1): 18915. https://doi.org/10.1038/s41598-021-98401-1
  21. Zhang XY, Guo CC, Yu YX, Xie L, Chang CQ (2020) Establishment of high-fat diet-induced obesity and insulin resistance model in rats. Beijing Da Xue Xue Bao Yi Xue Ban (Chinese) 52(3): 557–563. https://doi.org/10.19723/j.issn.1671-167X.2020.03.024
  22. Azemi AK, Siti-Sarah AR, Mokhtar SS, Rasool AHG (2022) Time-Restricted Feeding Improved Vascular Endothelial Function in a High-Fat Diet-Induced Obesity Rat Model. Vet Sci 9(5): 217. https://doi.org/10.3390/vetsci9050217
  23. Царева ИА, Иванова ГТ, Лобов ГИ (2022) Ранние изменения функционального состояния артерий и сосудов микроциркуляторного русла при моделировании метаболического синдрома. Рос физиол журн им ИМ Сеченова 108(9): 1134–1147. [Tsareva IA, Ivanova GT, Lobov GI (2022) Early Changes in the Functional State of the Arteries and Vessels of the Microcirculatory Bed in Modeling the Metabolic Syndrome. Russ J Physiol 108(9): 1134–1147. (In Russ)]. https://doi.org/10.31857/S0869813922090084
  24. Ledoux J, Werner EM, Brayden EJ, Nelson TM (2006) Calcium-activated potassium channels and the regulation of vascular tone. Physiology 21: 69–78. https://doi.org/10.1152/physiol.00040.2005
  25. Gamez-Mendez AM, Vargas-Robles H, Ríos A, Escalante B (2015) Oxidative stress-dependent coronary endothelial dysfunction in obese mice. PLoS One 10(9): 1–17. https://doi.org/10.1371/journal.pone.0138609
  26. Madkhali HA (2020) Morin attenuates high-fat diet induced-obesity related vascular endothelial dysfunction in Wistar albino rats. Saudi Pharm J 28(3): 300–307. https://doi.org/10.1016/j.jsps.2020.01.009
  27. Rubanyi GM (1991) Endothelium-derived relaxing and contracting factors. J Cell Biochem 46(1): 27–36. https://doi.org/10.1002/jcb.240460106
  28. Freed JK, Gutterman DD (2017) Communication Is Key: Mechanisms of Intercellular Signaling in Vasodilation. J Cardiovasc Pharmacol 69(5): 264–272. https://doi.org/10.1097/FJC.0000000000000463
  29. Dimassi S, Chahed K, Boumiza S, Canault M, Tabka Z, Laurant P, Riva C (2016) Role of eNOS- and NOX-containing microparticles in endothelial dysfunction in patients with obesity. Obesity 24: 1305–1312. https://doi.org/10.1002/oby.21508
  30. Schinzari F, Iantorno M, Campia U, Mores N, Rovella V, Tesauro M, Di Daniele N, Cardillo C (2015) Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome. Am J Physiol Endocrinol Metab 309(9): E787–E792. https://doi.org/10.1152/ajpendo.00278.2015
  31. Looft-Wilson RC, Ashley BS, Billig JE, Wolfert MR, Ambrecht LA, Bearden SE (2008) Chronic diet-induced hyperhomocysteinemia impairs eNOS regulation in mouse mesenteric arteries. Am J Physiol Regul Integr Comp Physiol 295(1): R59–R66. https://doi.org/10.1152/ajpregu.00833.2007
  32. Giles TD, Sander GE, Nossaman BD, Kadowitz PJ (2012) Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins. J Clin Hypertens (Greenwich) 14(4): 198–205. https://doi.org/10.1111/j.1751-7176.2012.00606.x
  33. Parkington HC, Coleman HA, Tare M (2004) Prostacyclin and endothelium-dependent hyperpolarization. Pharmacol Res 49(6): 509–514. https://doi.org/10.1016/j.phrs.2003.11.012
  34. Rubio-Ruiz ME, Pérez-Torres I, Diaz-Diaz E, Pavón N, Guarner-Lans V (2014) Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats. Acta Pharmacol Sin 35(11): 1364–1374. https://doi.org/10.1038/aps.2014.67
  35. Jin X, Satoh-Otonashi Y, Zamami Y, Takatori S, Hashikawa-Hobara N, Kitamura Y, Kawasaki H (2011) New molecular mechanisms for cardiovascular disease: contribution of endothelium-derived hyperpolarizing factor in the regulation of vasoconstriction in peripheral resistance arteries. J Pharmacol Sci 116(4): 332–336. https://doi.org/10.1254/jphs.10r30fm
  36. Mandalà M, Gokina N, Barron C, Osol G (2012) Endothelial-derived hyperpolarization factor (EDHF) contributes to PLGF-induced dilation of mesenteric resistance arteries from pregnant rats. J Vasc Res 49: 43–49. https://doi.org/10.1159/000329821
  37. Busse R, Edwards G, Félétou M, Fleming I, Vanhoutte PM, Weston AH (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23(8): 374–380. https://doi.org/10.1016/s0165-6147(02)02050-3
  38. Tykocki NR, Boerman EM, Jackson WF (2017) Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles. Compr Physiol 16; 7(2): 485–581. https://doi.org/10.1002/cphy.c160011
  39. Köhler R, Olivan-Viguera A, Wulff H (2016) Endothelial Small- and Intermediate-Conductance K Channels and Endothelium-Dependent Hyperpolarization as Drug Targets in Cardiovascular Disease. Adv Pharmacol 77: 65–104. https://doi.org/10.1016/bs.apha.2016.04.002
  40. Félétou M (2016) Endothelium-Dependent Hyperpolarization and Endothelial Dysfunction. J Cardiovasc Pharm 67: 373–387. https://doi.org/10.1097/FJC.0000000000000346
  41. Haddock RE, Grayson TH, Morris MJ, Howitt L, Chadha PS, Sandow SL (2011) Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms. PLoS One 6(1): e16423. https://doi.org/10.1371/journal.pone.0016423

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2.

Download (42KB)
Indexing metadata
3.

Download (71KB)
Indexing metadata
4.

Download (46KB)
Indexing metadata

Copyright (c) 2023 Г.Т. Иванова

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies