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PIII‐22
Author(s) -
Mayan H.,
Shaharabany M.,
Barak E.,
Holtzman E.,
Farfel Z.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.230
Subject(s) - furosemide , thiazide , endocrinology , medicine , distal convoluted tubule , hydrochlorothiazide , chemistry , reabsorption , renal sodium reabsorption , aquaporin 2 , epithelial sodium channel , renal medulla , sodium , kidney , cotransporter , homeostasis , diuretic , symporter , transporter , blood pressure , biochemistry , mechanical engineering , organic chemistry , water channel , engineering , inlet , gene
BACKGROUND WNK4 kinase is essential for the regulation of blood pressure and serum potassium, since its mutation produces the disorder familial hyperkalemia and hypertension (FHH). The molecular mechanism apparently involves interaction of WNK4 with the Na‐Cl cotransporter (NCCT) and the renal medulla potassium channel (ROMK). To better understand the role of WNK4 in the regulation of renal salt homeostasis, we modulated renal salt handling in rats, and measured renal WNK4 mRNA. METHODS Rats were treated by furosemide, hydrochlorothiazide, high salt diet (HSD) and low salt diet (LSD) for 7 days. Urine volume electrolytes and osmolarity were measured, and renal mRNA for WNK4 and GAPDH were quantitated by RT‐PCR. RESULTS Furosemide and thiazide caused diuresis eight and three times higher than control rats respectively. Urine sodium was two times higher with furosemide than control (18.3±2.1 vs 7.2±2.0 mmol/24hr, p<0.001) and only slightly and insignificantly higher than control after thiazide, (7.2±2.0 vs 8.8±0.5, p>0.05). Urine sodium was much higher in rats on HSD than on LSD, (18.3±2.1 vs 0.04±0.11, p<0.001). WNK4 mRNA rose by 55%, 65% and 200% in rats treated by HSD, furosemide and thiazide respectively. CONCLUSION Our results are compatible with the concept that a higher sodium content in the distal tubule, regardless of the means of achieving that, causes an increase in WNK4 expression. In addition, the thiazide‐induced dramatic rise in WNK4 mRNA may be caused by the thiazide‐bound NCCT. Clinical Pharmacology & Therapeutics (2005) 79 , P64–P64; doi: 10.1016/j.clpt.2005.12.230