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Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasone.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2009 Jul; Vol. 297 (1), pp. R93-9. Date of Electronic Publication: 2009 Apr 29. - Publication Year :
- 2009
-
Abstract
- 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 x mm(-1) x min(-1), 280 +/- 26 pmoles x mm(-1) x min(-1), and 191 +/- 21 pmoles x mm(-1) x 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.
- Subjects :
- Aging
Animals
Antihypertensive Agents pharmacology
Biological Transport
Blood Pressure drug effects
Dexamethasone administration & dosage
Female
Furosemide pharmacology
Gestational Age
Glucocorticoids administration & dosage
Hypertension metabolism
Hypertension physiopathology
Hypertension prevention & control
Injections, Intraperitoneal
Kinetics
Loop of Henle embryology
Loop of Henle metabolism
Male
Pregnancy
Rats
Rats, Sprague-Dawley
Sodium Potassium Chloride Symporter Inhibitors pharmacology
Sodium-Potassium-Chloride Symporters metabolism
Solute Carrier Family 12, Member 1
Chlorides metabolism
Dexamethasone toxicity
Diet, Protein-Restricted adverse effects
Glucocorticoids toxicity
Hypertension etiology
Loop of Henle drug effects
Maternal Nutritional Physiological Phenomena
Prenatal Exposure Delayed Effects
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 297
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 19403862
- Full Text :
- https://doi.org/10.1152/ajpregu.91006.2008