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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

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

Departments of ¹Pediatrics and ²Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Submitted 22 September 2006 ; accepted in final form 3 November 2006

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.

NHE3; in vitro microperfusion; volume absorption; acidification

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