Overexpression of chloride channel CLC-K2 mRNA in the renal medulla of Dahl salt-sensitive rats

J Hypertens. 2000 Sep;18(9):1289-95. doi: 10.1097/00004872-200018090-00015.

Abstract

Objective: The present study aimed to characterize the influence of salt intake on the gene expression of the kidney specific chloride channels CLC-K1 and CLC-K2 in the kidneys of salt-resistant and salt-sensitive Dahl rats.

Design: For this purpose Dahl salt-resistant (Dahl-R) and Dahl salt-sensitive rats (Dahl-S) were fed a low (0.02%), normal (0.6%) or high (4%) salt diet for 19 days and CLC-K1 and -K2 mRNA expression was semiquantitated in cortex, outer and inner medulla.

Methods: Kidneys were macroscopically dissected, total RNA was isolated according to the guanidinium-thiocyanate-phenol-chloroform method and messenger RNAs for the kidney specific chloride channels CLC-K1 and CLC-K2 were measured by ribonuclease protection assay.

Results: Systolic blood pressure in high salt-treated Dahl-S rats increased to 204 +/- 5 mmHg versus 150 +/- 7 mmHg in Dahl-S controls. Dahl R and low salt Dahl-S rats showed no increase in blood pressure. For CLC-K1 mRNA we found an order of abundance inner medulla >> outer medulla >> cortex. There was no difference in mRNA abundance between Dahl-R and -S, nor any effect of the rate of salt intake on CLC-K1 mRNA abundance in the different kidney zones. CLC-K2 mRNA expression in cortex and outer medulla was similar between Dahl-R and -S rats. In the inner medulla, however, CLC-K2 mRNA was 1.7-fold higher in Dahl-S than in Dahl-R rats. In the cortex we found no influence of salt intake on CLC-K2 mRNA. In outer and inner medulla of Dahl-R rats and Dahl-S rats high salt diet led to a marked downregulation of CLC-K2 mRNA expression. Consequently, CLC-K2 gene expression in the inner medulla was 2.2-fold higher in Dahl-S than in Dahl-R rats in states of high salt diet.

Conclusion: Given that the CLC-K2 chloride channel in the outer and inner medulla contributes to salt reabsorption, our findings would suggest that Dahl-S rats have an increased medullary salt reabsorption. This may contribute to the inability of these animals to excrete an increased salt load at a normal renal perfusion pressure leading to the development of hypertension.

MeSH terms

  • Animals
  • Anion Transport Proteins*
  • Chloride Channels / genetics*
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Hypertension, Renal / chemically induced
  • Hypertension, Renal / genetics*
  • Hypertension, Renal / physiopathology*
  • Kidney Cortex / physiology
  • Kidney Medulla / physiology*
  • Male
  • Membrane Proteins*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred Dahl
  • Ribonucleases
  • Sodium, Dietary / pharmacology

Substances

  • Anion Transport Proteins
  • CLCNKA protein, human
  • Chloride Channels
  • Clcnka protein, rat
  • Clcnkb protein, rat
  • Membrane Proteins
  • RNA, Messenger
  • Sodium, Dietary
  • Ribonucleases