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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]
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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 

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