Abstract: TH-OR074

Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic

Authors

  • Hirohama, Daigoro, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Fujita, Toshiro, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Ayuzawa, Nobuhiro, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Ueda, Kohei, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Nishimoto, Mitsuhiro, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Kawarazaki, Wakako, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Watanabe, Atsushi, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Shimosawa, Tatsuo, International University of Health and Welfare, Narita, Chiba, Japan
  • Marumo, Takeshi, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Shibata, Shigeru, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
Background

The renin-angiotensin-aldosterone system (RAAS) is known to play an important role in the control of fluid homeostasis and blood pressure during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, which increase levels of the Cl/HCO3 exchanger (pendrin) in β-intercalated cells and Na+-Cl cotransporter (NCC) in distal convoluted tubules; however, the independent roles of AngII and aldosterone in regulating these levels remain unclear.

Methods

In both C57BL/6J mice receiving a low-salt diet or AngII infusion and adrenalectomized mice receiving either AngII or co-administration of AngII and aldosterone, we evaluated membrane-protein abundance of pendrin, NCC and mineralocorticoid receptor (MR) phosphorylation, which selectively inhibits aldosterone binding in intercalated cells. We also measured blood pressure (BP) by radiotelemetry in pendrin-knockout and wild-type mice.

Results

A low-salt diet as well as AngII infusion upregulated NCC and pendrin levels, associated with decreased MR phosphorylation. Notably, a low-salt diet did not alter BP in wild-type mice, but significantly decreased BP in pendrin-knockout mice, suggesting the important role of pendrin in the regulation of BP. In adrenalectomized mice, AngII infusion again upregulated NCC, but did not affect pendrin expression despite the decreased MR phosphorylation. By contrast, AngII and aldosterone co-administration markedly elevated pendrin levels in adrenalectomized mice. AngII and aldosterone co-administration induced enhanced translocation of the MR to the nucleus in β-intercalated cells, whereas AngII alone did not.

Conclusion

Our results indicate that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest that pendrin contributes to maintaining normal BP in cooperation with NCC during activation of the RAAS by dietary salt restriction.