Skip to main content Accessibility help

High maternal sodium intake alters sex-specific renal renin–angiotensin system components in newborn Wistar offspring

  • D. R. R. Maia (a1), K. L. Lopes (a1), J. C. Heimann (a1) and L. N. S. Furukawa (a1)


This study aimed to evaluate the systemic and renal renin–angiotensin–aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.


Corresponding author

*Address for correspondence: L. N. S. Furukawa, Laboratory of Experimental Hypertension, Department of Internal Medicine, Nephrology Division, University of São Paulo School of Medicine, Av. Dr. Arnaldo, 455, 3° andar, sala 3342 São Paulo, SP 01246-903, Brazil. (Email


Hide All
1. Kagami, S, Border, WA, Miller, DE, et al. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-b expression in rat glomerular mesangial cells. J Clin Invest. 1994; 93, 24312437.
2. Chen, Y, Lasaitiene, D, Friberg, P. The renin–angiotensin system in kidney development. Acta Physiol Scand. 2004; 181, 529535.
3. Roberts, AB, McCune, BK, Sporn, MB. TGF-b: regulation of extracellular matrix. Kidney Int. 1992; 41, 557559.
4. Thiery, JP, Duband, JL, Dufour, S, et al. Role of fibronectin in embryogenesis. In Biology of Extracellular Matrix: Fibronectin ((ed. Mosher DF), 1989; pp. 181212. Academic Press: San Diego, CA.
5. Damkjær, M, Isaksson, GL, Stubbe, J, et al. Renal renin secretion as regulator of body fluid homeostasis. Eur J Physiol. 2013; 465, 153165.
6. Bie, P. Blood volume, blood pressure and total body sodium: internal signalling and output control. Acta Physiol. 2009; 195, 187196.
7. Graudal, NA, Galløe, AM, Garred, P. Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglycerides meta-analysis. JAMA. 1998; 279, 13831391.
8. Drenjančević-Perić, I, Jelaković, B, Lombard, JH, et al. High-salt diet and hypertension: focus on the renin-angiotensin system. Kidney Blood Press Res. 2011; 34, 111.
9. Cholewa, BC, Meister, CJ, Mattson, DL. Importance of the renin–angiotensin system in the regulation of arterial blood pressure in conscious mice and rats. Acta Physiol Scand. 2005; 183, 309320.
10. He, FJ, MacGregor, GA. Salt, blood pressure and the renin-angiotensin system. J Renin Angiotensin Aldosterone Syst. 2003; 4, 1116.
11. Contreras, RJ, Wong, DL, Henderson, R, et al. High dietary NaCl early in development enhances mean arterial pressure of adult rats. Physiol Behav. 2000; 71, 173181.
12. Contreras, RJ. Differences in perinatal NaCl exposure alters blood pressure levels of adult rats. Am J Physiol. 1989; 256(Pt 2), R70R77.
13. da Silva, AA, Noronha, LL, Oliveira, LB, et al. Renin angiotensin system function and blood pressure in adult rats after perinatal salt overload. Nutr Metab Cardiovasc Dis. 2003; 13, 133139.
14. Swenson, SJ, Speth, RC, Porter, JP. Effect of a perinatal high-salt diet on blood pressure control mechanisms in young Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol. 2004; 286, R764R770.
15. Porter, JP, King, SH, Honeycutt, AD. Prenatal high-salt diet in the Sprague-Dawley rat programs blood pressure and heart rate hyperresponsiveness to stress in adult female offspring. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R334R342.
16. Ramos, DR, Costa, NL, Jang, KLL, et al. Maternal high-sodium intake alters the responsiveness of the renin–angiotensin system in adult offspring. Life Sci. 2012; 90, 785792.
17. Ding, Y, Lv, J, Mao, C, et al. High-salt diet during pregnancy and angiotensin-related cardiac changes. J Hypertens. 2010; 28, 12901297.
18. Leandro, SM, Furukawa, LN, Shimizu, MH, et al. Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin–angiotensin system. Physiol Behav. 2008; 95, 551.
19. Jiménez, W, Martínez-Pardo, A, Arroyo, V, et al. Effect of the method of blood extraction on plasma levels of renin in the Wistar rat. Rev Esp Fisiol. 1985; 41, 299303.
20. Schenk, HD, Radke, J, Ensink, FB, et al. Interactions between renal and general hemodynamics in fentanyl, droperidol, ketamine, thiopental and in peridural anesthesia animal studies. Anaesthesiol Reanim. 1995; 20, 6070.
21. Giammattei, CE, Jack, WS, James, CR. Regulation of in vitro renin secretion by ANG II feedback manipulation in vivo in the ovine fetus. Am J Physiol. 1999; 277, R1230R1238.
22. Santos, RA, Krieger, EM, Greene, LJ. An improved fluorimetric assay of rat serum and plasma converting enzyme. Hypertension. 1985; 7, 244252.
23. Woods, LL, Ingelfinger, JR, Nyengaard, JR, et al. Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res. 2001; 49, 460467.
24. Vaccari, B, Mesquita, FF, Jose, AR, et al. Fetal kidney programming by severe food restriction: effects on structure, hormonal receptor expression and urinary sodium excretion in rats. J Renin Angiotensin Aldosterone Syst. 2015; 16, 3346.
25. Tufro-McReddie, A, Johns, DW, Geary, KM, et al. Angiotensin II type 1 receptor: role in renal growth and gene expression during normal development. Am J Physiol. 1994; 266(Pt 2), F911F918.
26. Yosipiv, IV, El-Dahr, SS. Activation of angiotensin-generating systems in the developing rat kidney. Hypertension. 1996; 27, 281286.
27. Yosipiv, IV, Dipp, S, El-Dahr, SS. Ontogeny of somatic angiotensin-converting enzyme. Hypertension. 1994; 23, 369374.
28. Balbi, APC, Costa, RS, Coimbra, TM. Postnatal renal development of rats from mothers that received increased sodium intake. Pediatr Nephrol. 2004; 19, 12121218.
29. Coelho, MS, Passadore, MD, Gasparetti, AL, et al. High- or low-salt diet from weaning to adulthood: effect on body weight, food intake and energy balance in rats. Nutr Metab Cardiovasc Dis. 2006; 16, 148155.
30. Lima, NKC, Lima, FB, Dos Santos, EA, et al. Effect of lifelong high- or low-salt intake on blood pressure, left ventricular mass and plasma insulin in Wistar rats. Am J Med Sci. 2006; 331, 309314.
31. Lumbers, ER. Functions of the renin-angiotensin system during development. Clin Exp Pharmacol Physiol. 1995; 22, 499505.
32. Berger, S, Bleich, M, Schmid, W, et al. Mineralocorticoid receptor knockout mice: pathophysiology of Na metabolism. Proc Natl Acad Sci. 1998; 95, 94249429.
33. Chevalier, RL, Thornhill, BA, Belmonte, DC, et al. Endogenous angiotensin II inhibits natriuresis following acute expansion in the neonatal rat. Am J Physiol Regul Integr Comp Physiol. 1996; 270, R393R397.
34. Tufro-McReddie, A, Johns, DW, Geary, KM, et al. Angiotensin II type 1 receptor: role in renal growth and gene expression during normal development. Am J Physiol. 1994; 266, F911F918.
35. Hazon, N, Henderson, IW. Effects of altered dietary sodium intake on hormonal profiles in salt-sensitive hypertensive rats. J Endocrinol. 1990; 127, 243248.
36. Gray, CC, Al-Dujaili, EA, Sparrow, AJ, et al. Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling. PLoS One. 2013; 8, e72682.
37. Kantorowicz, L, Valego, NK, Tang, L, et al. Plasma and renal renin concentrations in adult sheep after prenatal betamethasone exposure. Reprod Sci. 2008; 15, 831838.
38. Woods, LL, Ingelfinger, JR, Rasch, R. Modest maternal protein restriction fails to program adult hypertension in female rats. Am J Physiol Regul Integr Comp Physiol. 2005; 289, R1131R1136.
39. Chandran, M, Phillips, S, Ciaraldi, T, et al. Adiponectin: more than just another fat cell? Diabetes Care. 2003; 26, 24422450.
40. Zhou, D, Pan, YX. Pathophysiological basis for compromised health beyond generations: role of maternal high fat diet and low grade chronic inflammation. J Nutr Biochem. 2015; 26, 18.
41. Drake, A, McPherson, R, Godfrey, K, et al. An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth. Clin Endocrinol (Oxf). 2012; 77, 808815.
42. Allard, C, Desgagn, V, Patenaude, J, et al. Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns. Epigenetics. 2015; 10, 342351.
43. Hiejmans, B, Tobi, E, Stein, A, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105, 1704617049.
44. Lopez, JP, Gomez, AD, Sotomayer, RA, Mantilla, GD, Lopez, LJ. Maternal undernutrition and cardiometabolic disease: a Latin American perspective. BMC Med. 2015; 13, 293.
45. Hales, CN, Barker, DJ, Clark, PMS, et al. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991; 303, 10191022.
46. Barker, DJ, Winter, PD, Osmond, C, et al. Weight in infancy and death from ischemic heart disease. Lancet. 1989; 2, 577580.
47. Tarry-Adkins, JL, Ozanne, SE. Mechanisms of early life programming: current knowledge and future directions. Am J Clin Nutr. 2014; 94(Suppl.), 1765S1771S.


High maternal sodium intake alters sex-specific renal renin–angiotensin system components in newborn Wistar offspring

  • D. R. R. Maia (a1), K. L. Lopes (a1), J. C. Heimann (a1) and L. N. S. Furukawa (a1)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed