Abstract
Ouabain can normalize the blood pressure of the adult intrauterine growth restriction (IUGR) offspring through retaining the number of glomeruli of the IUGR newborn. However, the melioration of hemodynamic features coinciding with the improvement in cardiac structure and function is poorly understood. Intrauterine growth restriction was induced in pregnant rats with protein intake restriction, and ouabain was administrated using osmotic mini pumps from the second gestational day. The male offspring of the mothers with normal diet, low-protein diet, and low-protein diet added with ouabain treatment were randomly divided into 2 groups, one of which received normal diet and the other was treated with isocaloric 8% high-salt diet. We found that maternal malnutrition caused fetal growth retardation. At the end of a 40-week research, the offspring of the IUGR group presented high blood pressure and deteriorative cardiac performance and even worse in the offspring fed with 8% high-salt diet. Ouabain can normalize the blood pressure and improve the cardiac performance, even if following 8% high-salt diet challenge. Pathological and molecular analyses showed IUGR following 8% high-salt diet significantly increased the cardiac hypertrophy, whereas the unfavorable effects were ameliorated in the offspring treated with ouabain. Results suggest that the effects of ouabain on restoration of glomerular number in newborn and normalization of blood pressure during adulthood in IUGR male offspring can benefit the cardiac structure and function, especially under high-salt diet challenge.
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Bamfo JE, Odibo AO. Diagnosis and management of fetal growth restriction. J Pregnancy. 2011;2011:640715.
Moritz KM, Mazzuca MQ, Siebel AL, et al. Uteroplacental insufficiency causes a nephron deficit, modest renal insufficiency but no hypertension with ageing in female rats. J Physiol. 2009; 587(pt 11):2635-2646.
Baserga M, Bares AL, Hale MA, et al. Uteroplacental insufficiency affects kidney VEGF expression in a model of IUGR with compensatory glomerular hypertrophy and hypertension. Early Hum Dev. 2009;85(6):361-367.
Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, et al. A fetal cardiovascular score to predict infant hypertension and arterial remodeling in intrauterine growth restriction. Am J Obstet Gynecol. 2014;210(6):552.e1-552.e22.
Paixao AD, Alexander BT. How the kidney is impacted by the perinatal maternal environment to develop hypertension. Biol Reprod. 2013;89(6):144.
Ojeda NB, Hennington BS, Williamson DT, et al. Oxidative stress contributes to sex differences in blood pressure in adult growth-restricted offspring. Hypertension. 2012;60(1):114-122.
Ojeda NB, Intapad S, Royals TP, et al. Hypersensitivity to acute ANG II in female growth-restricted offspring is exacerbated by ovariectomy. Am J Physiol Regul Integr Comp Physiol. 2011; 301(4):R1199–R1205.
Baserga M, Kaur R, Hale MA, et al. Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11beta-hydroxysteroid dehydrogenase type 2 in a sex-specific manner. Am J Physiol Regul Integr Comp Physiol. 2010;299(1): R334–R342.
Hill JA, Olson EN. Cardiac plasticity. N Engl J Med. 2008; 358(13):1370-1380.
Katayama IA, Pereira RC, Dopona EP, et al. High-salt intake induces cardiomyocyte hypertrophy in rats in response to local angiotensin II type 1 receptor activation. J Nutr. 2014;144(10):1571-1578.
He FJ, Burnier M, Macgregor GA. Nutrition in cardiovascular disease: salt in hypertension and heart failure. Eur Heart J. 2011; 32(24):3073-3080.
Sanders MW, Fazzi GE, Janssen GM, Blanco CE, De Mey JG. High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats. Hypertension. 2005; 46(1):71-75.
Xie Z. Molecular mechanisms of Na/K-ATPase-mediated signal transduction. Ann N Y Acad Sci. 2003;986:497-503.
Xie Z, Askari A. Na(+)/K(+)-ATPase as a signal transducer. Eur J Biochem. 2002;269(10):2434-2439.
Li J, Zelenin S, Aperia A, Aizman O. Low doses of ouabain protect from serum deprivation-triggered apoptosis and stimulate kidney cell proliferation via activation of NF-kappaB. J Am Soc Nephrol. 2006;17(7):1848-1857.
Li J, Khodus GR, Kruusmagi M, et al. Ouabain protects against adverse developmental programming of the kidney. Nat Commun. 2010;1:42.
Zohdi V, Lim K, Pearson JT, Black MJ. Developmental programming of cardiovascular disease following intrauterine growth restriction: findings utilising a rat model of maternal protein restriction. Nutrients. 2014;7(1):119-152.
McMillen IC, Robinson JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005;85(2):571-633.
Barker DJ. Developmental origins of adult health and disease. J Epidemiol Community Health. 2004;58(2):114-115.
Zohdi V, Sutherland MR, Lim K, et al. Low birth weight due to intrauterine growth restriction and/or preterm birth: effects on nephron number and long-term renal health. Int J Nephrol. 2012;2012:136942.
Keijzer-Veen MG, Schrevel M, Finken MJ, et al. Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol. 2005;16(9):2762-2768.
Cantor EJ, Babick AP, Vasanji Z, Dhalla NS, Netticadan T. A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload. J Mol Cell Cardiol. 2005;38(5):777-786.
Nishikimi T, Yoshihara F, Horinaka S, et al. Chronic administration of adrenomedullin attenuates transition from left ventricular hypertrophy to heart failure in rats. Hypertension. 2003;42(5): 1034–1041.
Goyal R, Galffy A, Field SA, et al. Maternal protein deprivation: changes in systemic renin-angiotensin system of the mouse fetus. Reprod Sci. 2009;16(9):894-904.
Tsyvian PB, Markova TV, Mikhailova SV, Hop WC, Wladimiroff JW. Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus. Eur J Obstet Gynecol Reprod Biol. 2008;140(1):33-37.
Le Quang K, Bouchareb R, Lachance D, et al. Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34(10): 2283–2291.
Tu Y, Wan L, Bu L, et al. MicroRNA-22 downregulation by atorvastatin in a mouse model of cardiac hypertrophy: a new mechanism for antihypertrophic intervention. Cell Physiol Biochem. 2013;31(6):997-1008.
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Chen, L., Yue, J., Wu, H. et al. Ouabain Attenuates Cardiac Hypertrophy of Male Rat Offspring Exposed to Intrauterine Growth Restriction Following High-Salt Diet Challenge. Reprod. Sci. 22, 1587–1596 (2015). https://doi.org/10.1177/1933719115589412
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DOI: https://doi.org/10.1177/1933719115589412