Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-24T12:12:34.090Z Has data issue: false hasContentIssue false
  • English
  • Français

Up-regulation of renal renin–angiotensin system and inflammatory mechanisms in the prenatal programming by low-protein diet: beneficial effect of the post-weaning losartan treatment

Published online by Cambridge University Press:  06 May 2018

I. K. M. Watanabe ,
Z. P. Jara ,
R. A. Volpini ,
M. d. C. Franco ,
F. F. Jung  and
D. E. Casarini
I. K. M. Watanabe
Affiliation:
Department of Medicine, Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil
Z. P. Jara
Affiliation:
Department of Medicine, Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil
R. A. Volpini
Affiliation:
Department of Nephrology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
M. d. C. Franco
Affiliation:
Department of Medicine, Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil
F. F. Jung
Affiliation:
Department of Pediatrics, Georgetown University, Washington, DC, USA
D. E. Casarini*
Affiliation:
Department of Medicine, Nephrology Division, Federal University of Sao Paulo, Sao Paulo, Brazil
*
Address for correspondence: D. E. Casarini, Division of Nephrology, School of Medicine, Federal University of São Paulo, Rua Botucatu, 740, São Paulo, SP 04023-062, Brazil. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Previous studies have shown that the renin–angiotensin system (RAS) is affected by adverse maternal nutrition during pregnancy. The aim of this study was to investigate the effects of a maternal low-protein diet on proinflammatory cytokines, reactive oxygen species and RAS components in kidney samples isolated from adult male offspring. We hypothesized that post-weaning losartan treatment would have beneficial effects on RAS activity and inflammatory and oxidative stress markers in these animals. Pregnant Sprague–Dawley rats were fed with a control (20% casein) or low-protein diet (LP) (6% casein) throughout gestation. After weaning, the LP pups were randomly assigned to LP and LP-losartan groups (AT1 receptor blockade: 10 mg/kg/day until 20 weeks of age). At 20 weeks of age, blood pressure levels were higher and renal RAS was activated in the LP group. We also observed several adverse effects in the kidneys of the LP group, including a higher number of CD3, CD68 and proliferating cell nuclear antigen-positive cells and higher levels of collagen and reactive oxygen species in the kidney. Further, our results revealed that post-weaning losartan treatment completely abolished immune cell infiltration and intrarenal RAS activation in the kidneys of LP rats. The prevention of augmentation of angiotensin (Ang II) concentration abolished inflammatory and fibrotic events, indicating that Ang II via the AT1 receptor is essential for pathological initiation. Our results suggest that the prenatal programming of hypertension is dependent on the up-regulation of local RAS and presence of immune cells in the kidney.

Keywords

inflammationlosartanlow-protein dietprenatal programmingrenin–angiotensin system
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 5 , October 2018 , pp. 530 - 535
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Eriksson, JG. Developmental Origins of Health and Disease – from a small body size at birth to epigenetics. Ann Med. 2016; 48, 456–467.Google Scholar
2. Chavatte-Palmer, P, Tarrade, A, Rousseau-Ralliard, D. Diet before and during pregnancy and offspring health: the importance of animal models and what can be learned from them. Int J Environ Res Public Health. 2016; 13, pii. E586.Google Scholar
3. Lea, AJ, Tung, J, Archie, EA, Alberts, SC. Developmental plasticity: bridging research in evolution and human health. Evol Med Public Health. 2017; 2017, 162–175.Google Scholar
4. Kett, MM, Denton, KM. Renal programming: cause for concern? Am J Physiol Regul Integr Comp Physiol. 2011; 300, R791–R803.Google Scholar
5. Paixao, AD, Alexander, BT. How the kidney is impacted by the perinatal maternal environment to develop hypertension. Biol Reprod. 2013; 89, 144.Google Scholar
6. Grigore, D, Ojeda, NB, Robertson, EB, et al. Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R804–R811.Google Scholar
7. Sherman, RC, Langley-Evans, SC. Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat. Clin Sci. 2000; 98, 269–275.Google Scholar
8. Nguyen Dinh Cat, A, Montezano, AC, Burger, D, Touyz, RM. Angiotensin II, NADPH oxidase, and redox signaling in the vasculature. Antioxid Redox Signal. 2013; 19, 1110–1120.Google Scholar
9. Franco Mdo, C, Akamine, EH, Di Marco, GS, et al. NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin-angiotensin system. Cardiovasc Res. 2003; 59, 767–775.Google Scholar
10. Ruiz-Ortega M, Ruperez M, Lorenzo O, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl. 2002; 82, S12–S22. https://doi.org/10.1046/j.1523-1755.62.s82.4.x(82).Google Scholar
11. Kintscher, U, Wakino, S, Kim, S, et al. Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human monocytes. Hypertension. 2001; 37(Pt 2), 587–593.Google Scholar
12. Jurewicz, M, McDermott, DH, Sechler, JM, et al. Human T and natural killer cells possess a functional renin-angiotensin system: further mechanisms of angiotensin II-induced inflammation. J Am Soc Nephrol. 2007; 18, 1093–1102.Google Scholar
13. Pastore, L, Tessitore, A, Martinotti, S, et al. Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo. Circulation. 1999; 100, 1646–1652.Google Scholar
14. Pueyo, ME, Gonzalez, W, Nicoletti, A, et al. Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol. 2000; 20, 645–651.Google Scholar
15. Hoch, NE, Guzik, TJ, Chen, W, et al. Regulation of T-cell function by endogenously produced angiotensin II. Am J Physiol Regul Integr Comp Physiol. 2009; 296, R208–R216.Google Scholar
16. Vehaskari, VM, Aviles, DH, Manning, J. Prenatal programming of adult hypertension in the rat. Kidney Int. 2001; 59, 238–245.Google Scholar
17. Woods, LL, Weeks, DA, Rasch, R. Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int. 2004; 65, 1339–1348.Google Scholar
18. Carey, RM. The intrarenal renin-angiotensin system in hypertension. Adv Chronic Kidney Dis. 2015; 22, 204–210.Google Scholar
19. Ingert, C, Grima, M, Coquard, C, Barthelmebs, M, Imbs, JL. Contribution of angiotensin II internalization to intrarenal angiotensin II levels in rats. Am J Physiol Renal Physiol. 2002; 283, F1003–F1010.Google Scholar
20. Crowley, SD, Frey, CW, Gould, SK, et al. Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension. Am J Physiol Renal Physiol. 2008; 295, F515–F524.Google Scholar
21. Stewart, T, Jung, FF, Manning, J, Vehaskari, VM. Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension. Kidney Int. 2005; 68, 2180–2188.Google Scholar
22. Guzik, TJ, Hoch, NE, Brown, KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007; 204, 2449–2460.Google Scholar
23. McMaster, WG, Kirabo, A, Madhur, MS, Harrison, DG. Inflammation, immunity, and hypertensive end-organ damage. Circulation Res. 2015; 116, 1022–1033.Google Scholar
24. Araujo, M, Wilcox, CS. Oxidative stress in hypertension: role of the kidney. Antioxid Redox Signal. 2014; 20, 74–101.Google Scholar