Upregulation of renal BSC1 and TSC in prenatally programmed hypertension

Am J Physiol Renal Physiol. 2002 Jul;283(1):F202-6. doi: 10.1152/ajprenal.00358.2001.


Prenatal factors, especially intrauterine growth retardation, have been shown to correlate with the risk of essential hypertension in adult life, but the mechanisms are unknown. An experimental model of prenatal programming of hypertension in the rat, induced by a maternal low-protein diet during pregnancy, was employed to study the role of renal Na reabsorption in the pathogenesis. The abundance of the apical Na transporter type III Na/H exchanger (NHE3), bumetanide-sensitive Na-K-2Cl cotransporter (BSC1), thiazide-sensitive Na-Cl cotransporter (TSC), and the amiloride-sensitive epithelial Na channel (ENaC) was determined by semiquantitative immunoblotting in kidneys from the offspring at 4 wk of age, before hypertension became manifest. There were no significant differences between the experimental and control rats in the abundance of NHE3 or any of the ENaC subunits. In contrast, the quantity of BSC1 in the experimental group was increased to 302% of control (P < 0.001) and that of TSC to 157% of control (P < 0.05). Determination of specific mRNA levels by ELISA-linked RT-PCR revealed a significantly increased BSC1 mRNA at 1 day (P < 0.01), 4 wk (P < 0.01), and 8 wk (P < 0.001) of age, and a significantly increased TSC mRNA at 4 wk of age (P < 0.05) in the experimental group. The results suggest that prenatal programming of hypertension involves transcriptional upregulation of Na transport in thick ascending limb and distal convoluted tubule.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure
  • Body Weight
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Diet, Protein-Restricted
  • Female
  • Gene Expression / physiology
  • Hypertension, Renal / metabolism*
  • Loop of Henle / embryology*
  • Loop of Henle / metabolism
  • Natriuresis / physiology
  • Pregnancy
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / genetics*
  • Receptors, Drug / metabolism*
  • Sodium / metabolism
  • Sodium Chloride Symporters
  • Sodium-Potassium-Chloride Symporters / genetics*
  • Sodium-Potassium-Chloride Symporters / metabolism*
  • Solute Carrier Family 12, Member 1
  • Solute Carrier Family 12, Member 3
  • Symporters*
  • Up-Regulation / physiology


  • Carrier Proteins
  • RNA, Messenger
  • Receptors, Drug
  • Slc12a1 protein, rat
  • Slc12a3 protein, rat
  • Sodium Chloride Symporters
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 1
  • Solute Carrier Family 12, Member 3
  • Symporters
  • thiazide receptor
  • Sodium