Role of postnatal dietary sodium in prenatally programmed hypertension

Abstract

In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43–49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal “reprogramming” of the hypertension.

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Acknowledgements

Support for this study was provided by National Heart, Lung, and Blood Institute Grant RO1 HL66158. This paper was presented in part as an abstract at the Annual Meeting of the American Society of Nephrology in November 2007.

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Correspondence to V. Matti Vehaskari.

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Stewart, T., Ascani, J., Craver, R.D. et al. Role of postnatal dietary sodium in prenatally programmed hypertension. Pediatr Nephrol 24, 1727–1733 (2009). https://doi.org/10.1007/s00467-009-1196-8

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Keywords

  • Developmental origins
  • Oxidative stress
  • Salt-sensitivity
  • Tubulointerstitial injury