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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/R93    most recent 91006.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Dagan, A. Articles by Baum, M. PubMed PubMed Citation Articles by Dagan, A. Articles by Baum, M.

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Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasone

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

Submitted 12 December 2008 ; accepted in final form 25 April 2009

Prenatal administration of dexamethasone and a low-protein diet has been shown to result in hypertension in the offspring when they are adults. The cause for the hypertension is unknown. The purpose of this study was to examine whether there was prenatal programming of thick ascending limb transport. Rats were administered either dexamethasone for 4 days (0.2 mg/kg body wt) by intraperitoneal injection daily between the 15th and 18th day of gestation, or they were fed a low-protein diet (6% protein) or an isocaloric normal protein diet (20% protein) from day 12 gestation until birth. The offspring were studied as adults. Prenatal dexamethasone and dietary protein deprivation resulted in an increase in blood pressure. Offspring of mothers fed a low-protein diet had an increase in medullary but not cortical bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) protein abundance (P < 0.01). There was not a statistically significant increase in medullary NKCC2 by prenatal dexamethasone (P = 0.07). Both prenatal administration of dexamethasone and a low-protein diet resulted in an increase in medullary thick ascending limb chloride transport compared with control (298 ± 33 pmoles·mm^–1·min^–1, 280 ± 26 pmoles·mm^–1·min^–1, and 191 ± 21 pmoles·mm^–1·min^–1, respectively P < 0.05). There was a higher lumen-positive transepithelial potential difference in the prenatal dexamethasone and low-protein group compared with control as well. Administration of furosemide for 24 h resulted in a decrease in blood pressure in the low-protein group but not the control group. This study demonstrates that insults administered to the fetus can program altered sodium transport. Increased tubular sodium transport is a likely cause for the hypertension by prenatal programming.

prenatal programming; hypertension; microperfusion; furosemide