Intrauterine growth restriction does not lead to pronounced changes in the regulation of arterial contractile responses in rats in the early postnatal period

Cover Page

Cite item

Full Text

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

Abstract

Intrauterine growth retardation (IUGR) is one of the most common pathologies of pregnancy. As a result of this pathology, the functioning of many systems, including the cardiovascular system, is disrupted. In adult animals who have suffered IUGR, the contribution of procontractile mechanisms regulating vascular tone (for example, the Rho-kinase signaling pathway) increases, and the contribution of anticontractile mechanisms (for example, endothelial NO), on the contrary, decreases, which can lead to vasospasm and impaired blood supply to organs. Since NO and Rho-kinase have a pronounced vasomotor role in early postnatal ontogenesis, the purpose of this work was to assess the influence of IUGR on the contribution of these mechanisms to the regulation of arterial contractile responses in early postnatal ontogenesis. IUGR was modeled by limiting the amount of food consumed by females (by 50%) from the 11th day of pregnancy until birth. In offspring aged 11 - 12 days, the reactions of the isolated saphenous artery were studied in isometric mode, and the content of mRNA and proteins of interest in this artery was also assessed. IUGR did not lead to a change in the reactivity of the arteries of the offspring to the α1-adrenergic receptor agonist methoxamine. The increase in contractile responses to methoxamine in the presence of the NO-synthase inhibitor L-NNA, as well as the expression levels of eNOS (mRNA and protein) and arginase-2 (mRNA) were not changed in the arteries of IUGR rats, while the sensitivity of the arteries to the exogenous NO donor DEA /NO was higher in IUGR compared to control rat pups. Despite the relatively low content of RhoA and Rho-kinase II proteins in the arterial tissue of rat pups from the IUGR group, the decrease in contractile responses under the influence of the Rho-kinase inhibitor Y27632 was equally pronounced in the arteries of rat pups from two experimental groups. Thus, IUGR, caused by maternal nutritional restriction during pregnancy, does not lead to pronounced changes in the regulation of systemic vascular tone in the early postnatal period.

About the authors

А. А. Shvetsova

Lomonosov Moscow State University

Author for correspondence.
Email: Dina.Gaynullina@gmail.com
Russian Federation, Moscow

Е. К. Selivanova

Lomonosov Moscow State University; ChemRar Research and Development Institute

Email: Dina.Gaynullina@gmail.com
Russian Federation, Moscow; Khimki, Moscow Region

L. D. Shilova

Lomonosov Moscow State University

Email: Dina.Gaynullina@gmail.com
Russian Federation, Moscow

О. S. Tarasova

Lomonosov Moscow State University; Institute of Biomedical Problems of the Russian Academy of Sciences

Email: Dina.Gaynullina@gmail.com
Russian Federation, Moscow; Moscow

D. К. Gaynullina

Lomonosov Moscow State University

Email: Dina.Gaynullina@gmail.com
Russian Federation, Moscow

References

  1. Yzydorczyk C, Armengaud JB, Peyter AC, Chehade H, Cachat F, Juvet C, Siddeek B, Simoncini S, Sabatier F, Dignat-George F, Mitanchez D, Simeoni U (2017) Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches. J Dev Orig Health Dis 8: 448–464. https://doi.org/10.1017/S2040174417000265
  2. Freije WA, Thamotharan S, Lee R, Shin B, Devaskar SU (2015) The Hepatic Transcriptome of Young Suckling and Aging Intrauterine Growth Restricted Male Rats. J Cell Biochem 116: 566–579. https://doi.org/10.1002/jcb.25008
  3. Gibson LC, Shin B, Dai Y, Freije W, Kositamongkol S, Cho J, Devaskar SU (2015) Early leptin intervention reverses perturbed energy balance regulating hypothalamic neuropeptides in the pre‐ and postnatal calorie‐restricted female rat offspring. J Neurosci Res 93: 902–912. https://doi.org/10.1002/jnr.23560
  4. Zanardo V, Visentin S, Trevisanuto D, Bertin M, Cavallin F, Cosmi E (2013) Fetal aortic wall thickness: a marker of hypertension in IUGR children? Hypertens Res 36: 440–443. https://doi.org/10.1038/hr.2012.219
  5. Visentin S, Grumolato F, Battista G, Di B, Grisan E, Cosmi E (2014) Early origins of adult disease : Low birth weight and vascular remodeling. Atherosclerosis 237: 391–399. https://doi.org/10.1016/j.atherosclerosis.2014.09.027
  6. Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, Sachdev HS (2008) Maternal and Child Undernutrition: consequences for adult health and human capital. Lancet 371: 340–357. https://doi.org/10.1016/S0140-6736(07)61692-4
  7. Torrens C, Brawley L, Anthony FW, Dance CS, Dunn R, Jackson AA, Poston L, Hanson MA (2006) Folate Supplementation During Pregnancy Improves Offspring Cardiovascular Dysfunction Induced by Protein Restriction. Hypertension 47: 982–987. https://doi.org/10.1161/01.HYP.0000215580.43711.d1
  8. Franco M do C, Fortes ZB, Akamine EH, Kawamoto EM, Scavone C, De Britto LRG, Muscara MN, Teixeira SA, Tostes RCA, Carvalho MHC, Nigro D (2004) Tetrahydrobiopterin improves endothelial dysfunction and vascular oxidative stress in microvessels of intrauterine undernourished rats. J Physiol 558: 239–248. https://doi.org/10.1113/jphysiol.2004.064055
  9. Oliveira V, de Souza LV, Fernandes T, Junior SDS, de Carvalho MHC, Akamine EH, Michelini LC, de Oliveira EM, Franco M do C (2017) Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function. J Dev Orig Health Dis 8: 665–673. https://doi.org/10.1017/S2040174417000484
  10. Torrens C, Brawley L, Barker AC, Itoh S, Poston L, Hanson MA (2003) Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring. J Physiol 547: 77–84. https://doi.org/10.1113/jphysiol.2002.026120
  11. Rock CR, White TA, Piscopo BR, Sutherland AE, Pham Y, Camm EJ, Sehgal A, Polglase GR, Miller SL, Allison BJ (2023) Cardiovascular decline in offspring during the perinatal period in an ovine model of fetal growth restriction. Am J Physiol Hear Circ Physiol 325: H1266–H1278. https://doi.org/10.1152/ajpheart.00495.2023
  12. Selivanova EK, Shvetsova AA, Shilova LD, Tarasova OS, Gaynullina DK (2021) Intrauterine growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats. Sci Rep 11: 1–11. https://doi.org/10.1038/s41598-021-93491-3
  13. Gaynullina DK, Schubert R, Tarasova OS (2019) Changes in endothelial nitric oxide production in systemic vessels during early ontogenesis – A key mechanism for the perinatal adaptation of the circulatory system. Int J Mol Sci 20: 1–12. https://doi.org/10.3390/ijms20061421
  14. Gaynullina D, Lubomirov LT, Sofronova SI, Kalenchuk VU, Gloe T, Pfitzer G, Tarasova OS, Schubert R (2013) Functional remodelling of arterial endothelium during early postnatal development in rats. Cardiovasc Res 99: 612–621. https://doi.org/10.1093/cvr/cvt138
  15. Sofronova SI, Borzykh AA, Gaynullina DK, Kuzmin IV, Shvetsova AA, Lukoshkova EV, Tarasova OS (2016) Endothelial nitric oxide weakens arterial contractile responses and reduces blood pressure during early postnatal development in rats. Nitric Oxide – Biol Chem 55–56: 1–9. https://doi.org/10.1016/j.niox.2016.02.005
  16. Puzdrova VA, Kudryashova TV, Gaynullina DK, Mochalov SV, Aalkjaer C, Nilsson H, Vorotnikov AV, Schubert R, Tarasova OS (2014) Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+ sensitivity during early post-natal development in rats. Acta Physiol 212: 128–141. https://doi.org/10.1111/apha.12331
  17. Mochalov SV, Tarasova NV, Kudryashova TV, Gaynullina DK, Kalenchuk VU, Borovik AS, Vorotnikov AV, Tarasova OS, Schubert R (2018) Higher Ca2+-sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity. Acta Physiol 223: 1–15. https://doi.org/10.1111/apha.13044
  18. Štulcová B (1977) Postnatal Development of Cardiac Output Distribution Measured by Radioactive Microspheres in Rats. Neonatology 32: 119–124. https://doi.org/10.1159/000241004
  19. Mulvany MJ, Halpern W (1977) Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41: 19–26. https://doi.org/10.1161/01.RES.41.1.19
  20. Тарасова ОС, Гайнуллина ДК (2017) Rho-киназа как ключевой участник регуляции тонуса сосудов в норме и при сосудистых расстройствах. Артер гипертен 23: 383–394. [Tarasova OS, Gainullina DK (2017) Rho-kinase as a key participant in the regulation of vascular tone in health and in vascular disorders. Arter hyperten 23: 383–394. (In Russ)]. https://doi.org/10.18705/1607-419X-2017-23-5-383-394
  21. Garg M, Thamotharan M, Dai Y, Lagishetty V, Matveyenko AV, Lee WNP, Devaskar SU (2013) Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats. Endocrinology 154: 102–113. https://doi.org/10.1210/en.2012-1640
  22. Garg M, Thamotharan M, Dai Y, Thamotharan S, Shin B, Stout D, Devaskar SU (2012) Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth – Restricted Offspring From Obesity. Diabetes 61: 1391–1398. https://doi.org/10.2337/db11-1347
  23. Thamotharan M, Shin B, Suddirikku DT, Thamotharan S, Garg M, Devaskar SU (2005) GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring. Am J Physiol Metab 288: E935–E947. https://doi.org/10.1152/ajpendo.00342.2004
  24. Zamojska J, Niewiadomska-Jarosik K, Kierzkowska B, Gruca M, Wosiak A, Smolewska E (2023) Lipid Profile in Children Born Small for Gestational Age. Nutrients 15. https://doi.org/10.3390/nu15224781
  25. Brandes RP, Kim DY, Schmitz-Winnenthal FH, Amidi M, Gödecke A, Mülsch A, Busse R (2000) Increased nitrovasodilator sensitivity in endothelial nitric oxide synthase knockout mice: Role of soluble guanylyl cyclase. Hypertension 35: 231–236. https://doi.org/10.1161/01.hyp.35.1.231
  26. Ohashi Y, Kawashima S, Hirata KI, Yamashita T, Ishida T, Inoue N, Sakoda T, Kurihara H, Yazaki Y, Yokoyama M (1998) Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. J Clin Invest 102: 2061–2071. https://doi.org/10.1172/JCI4394
  27. Krause BJ, Peñaloza E, Candia A, Cañas D, Hernández C, Arenas GA, Peralta-Scholz MJ, Valenzuela R, García-Herrera C, Herrera EA (2019) Adult vascular dysfunction in foetal growth-restricted guinea-pigs is associated with a neonate-adult switching in Nos3 DNA methylation. Acta Physiol 227: 1–13. https://doi.org/10.1111/apha.13328
  28. Akopov SE, Zhang L, Pearce WJ (1998) Regulation of Ca2+ sensitization by PKC and rho proteins in ovine cerebral arteries: Effects of artery size and age. Am J Physiol Hear Circ Physiol 275: 930–939. https://doi.org/10.1152/ajpheart.1998.275.3.h930
  29. Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: Modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83: 1325–1358. https://doi.org/10.1152/physrev.00023.2003

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Russian Academy of Sciences