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


METHODS
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.


CONCLUSIONS
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.
Castrop
H
H
Institut für Physiologie, Universität Regensburg, Germany.
Krämer
B K
BK
Riegger
G A
GA
Kurtz
A
A
Wolf
K
K
D000818:Animals; D027321:Anion Transport Proteins; D018118:Chloride Channels / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006977:Hypertension, Renal / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D007672:Kidney Cortex / Q000502:physiology; D007679:Kidney Medulla / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D012260:Ribonucleases; D012982:Sodium, Dietary / Q000494:pharmacology
D027321:Anion Transport Proteins; C489932:CLCNKA protein, human; D018118:Chloride Channels; C082118:Clcnka protein, rat; C486572:Clcnkb protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D012982:Sodium, Dietary; D012260:Ribonucleases