OS 21-04 UPREGULATION OF CLAUDIN-4 IN THE KIDNEY OF DAHL SALT-SENSITIVE RATS

Abstract

Objective: Claudins are tight junction proteins that regulate paracellular permeability of renal epithelia, and renal paracellular sodium chloride permeability may be essential to salt homeostasis and blood pressure control. A previous study has shown that the collecting duct-specific claudin-4 knockout animals develop hypotension due to profound renal wasting of chloride. This study was undertaken to investigate whether claudins have a role in the hypertension of Dahl salt-sensitive (DS) rats. Design and Method: Male DS and Dahl salt-resistant (DR) rats, 6 of each, were maintained on an 8% NaCl-containing rodent diet for 4 weeks. Systolic blood pressure (SBP) and plasma and urine electrolytes were weekly measured. At the end of animal experiment, kidneys were harvested for immunoblotting and quantitative PCR analysis of tight junction proteins including claudin-2, claudin-4, claudin-7, claudin-8, occludin, and ZO-1. Results: SBP was significantly higher in DS than in DR rats at the 1st to 4th week of the animal experiment. At the 1st and 2nd week, urine sodium and chloride excretion were significantly reduced in DS as compared with DR rats. At the 2nd week, DS rats had lower concentrations of plasma sodium and chloride than DR rats. The body weight measured at the end of animal experiment was lower in DS than in DR rats. In the kidney, claudin-4 protein and mRNA were significantly increased in DS as compared with DR rats. On the other hand, occludin protein and mRNA were significantly decreased in DS as compared with DR rats. The expressions of claudin-2, claudin-7, and claudin-8 were not significantly different between the two groups. Conclusions: In DS rats, salt-sensitive hypertension was associated with differential changes in renal tight junction protein expression. Upregulation of claudin-4 might increase paracellular sodium chloride transport in the kidney, resulting in impaired pressure natriuresis in DS rats.