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Abstract: FR-PO315

The Role of Renal Claudin-4 Protein in Salt-Induced Hypertension of Spontaneous Hypertensive and Dahl Salt Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Kim, Gheun-Ho, Hanyang University, Seoul, Korea (the Republic of)
  • Kim, Sua, Hanyang University, Seoul, Korea (the Republic of)
  • Jo, Chor ho, Hanyang University, Seoul, Korea (the Republic of)
Background

Claudin proteins in the kidney act as Na+ barrier or Cl- channel, and hypotension was reported from renal claudin-4 knockout mice due to urinary Cl- loss. Our previous study showed that salt-sensitive hypertension was associated with upregulation ofclaudin-4 in Dahl salt rats (DSR). Here we extended our work to see if any changes in renal claudin proteins precede the development of salt-sensitive hypertension in spontaneous hypertensive rats (SHR) and DSR.

Methods

Time course studies were undertaken over two weeks for SHR and one week for DSR. SHR were randomly divided into normal salt-loaded (SN, n=4) and high salt-loaded (SH, n=4) rats at each time point. High salt was offered with 8% NaCl diet. Wistar Kyoto rats (WKR) served as controls and were given normal salt diet. DSR were classified into salt-resistant (SR, n=6) and salt-sensitive (SS, n=6) rats, and both groups were given 8% NaCl diet. Systolic blood pressure (SBP), urine sodium excretion, and renal protein expression of claudin-2, claudin-4, claudin-7, claudin-8, and claudin-10 were serially followed.

Results

At baseline, SBP was higher in SHR than in WKR (137 + 1 vs. 118 + 1 mmHg, P<0.05). SBP was not different between SN and SH at Day 7, but was higher in SH than in SN (162 + 1 vs. 156 + 1 mmHg, P<0.05) at Day 14. WKR had lower SBPs throughout the period (114 + 1 mmHg at Day 14). At baseline, claudin-4 (123 + 1 vs. 100 + 2%, P<0.05) expression increased in SHR compared with WKR. The expression of claudin-4 was not different between SN and SH at baseline, but increased in SH compared with SN from Day 7 (185 + 4 vs. 130 + 2%, P<0.05) to Day 14. In DSR, SBP was not significantly different between SR and SS through Day 3, but increased in SScompared with SR (141 + 2 vs. 119 + 1 mmHg, P<0.05) at Day 7. From baseline (174 + 3 vs. 100 + 3%, P<0.05) to Day 3 (240 + 4 vs. 100 + 3%, P<0.05), claudin-4 expression increased in SS compared with SR. Immunofluorescence localization of claudins in the kidney was compatible with the results of immunoblot analysis.

Conclusion

In response to high salt intake, the increase in renal claudin-4 protein preceded the elevation of SBP in both SHR and DSR. Claudin-4 expression also increased in SHR compared with WKR. These findings suggest the contributory role of renal claudin-4 in salt-sensitive hypertension.

Funding

  • Government Support - Non-U.S.