Prenatal programming of rat proximal tubule Na+/H+ exchanger by dexamethasone

Amit Dagan, Jyothsna Gattineni, Vodi Cook, Michel Baum

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58 Scopus citations


Prenatal administration of dexamethasone causes hypertension in rats when they are studied as adults. Although an increase in tubular sodium reabsorption has been postulated to be a factor programming hypertension, this has never been directly demonstrated. The purpose of this study was to examine whether prenatal programming by dexamethasone affected postnatal proximal tubular transport. Pregnant Sprague-Dawley rats were injected with intraperitoneal dexamethasone (0.2 mg/kg) daily for 4 days between the 15th and 18th days of gestation. Prenatal dexamethasone resulted in an elevation in systolic blood pressure when the rats were studied at 7-8 wk of age compared with vehicle-treated controls: 131 ± 3 vs. 115 ± 3 mmHg (P < 0.001). The rate of proximal convoluted tubule volume absorption, measured using in vitro microperfusion, was 0.61 + 0.07 nl·mm-1·min -1 in control rats and 0.93+ 0.07 nl·mm -1·min-1 in rats that received prenatal dexamethasone (P < 0.05). Na+/H+ exchanger activity measured in perfused tubules in vitro using the pH-sensitive dye BCECF showed a similar 50% increase in activity in proximal convoluted tubules from rats treated with prenatal dexamethasone. Although there was no change in abundance of NHE3 mRNA, the predominant luminal proximal tubule Na+/H + exchanger, there was an increase in NHE3 protein abundance on brush-border membrane vesicles in 7- to 8-wk-old rats receiving prenatal dexamethasone. In conclusion, prenatal administration of dexamethasone in rats increases proximal tubule transport when rats are studied at 7-8 wk old, in part by stimulating Na+/H+ exchanger activity. The increase in proximal tubule transport may be a factor mediating the hypertension by prenatal programming with dexamethasone.

Original languageEnglish (US)
Pages (from-to)R1230-R1235
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
StatePublished - Mar 2007


  • Acidification
  • In vitro microperfusion
  • NHE3
  • Volume absorption

ASJC Scopus subject areas

  • General Medicine


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