ALTERED RENALTIGHT JUNCTION PROTEIN EXPRESSION AND PRESSURE NATRIURESIS IN DAHL SALT-SENSITIVE RATS

Abstract

Introduction and Aims: Altered pressure natriuresis is an important mechanism of hypertension, but it remains elusive at a molecular level. We hypothesized that tight junction (TJ) may have a role in pressure natriuresis because paracelullar NaCl transport affects interstitial hydrostatic pressure in the kidney.

Methods: To assess the association of salt-sensitive hypertension with altered renal TJ protein expression, Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats were put on an 8% NaCl-containing rodent diet for 4 weeks. Systolic blood pressure (SBP) and urine sodium excretion were weekly measured, and kidneys were harvested for immunoblotting and quantitative PCR analysis at the end of animal experiment.

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 excretion was significantly reduced in DS as compared with DR rats. However, it had no significant difference between the two groups at the end of animal experiment. 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 TJ protein expression. Both upregulation of claudin-4 and downregulation of occludin might increase paracellular NaCl transport in the kidney, resulting in impaired pressure natriuresis in DS rats.