Description: Background Angiotensin II type 1 receptor (AT1R)–associated protein (ATRAP; Agtrap gene) promotes AT1R internalization along with suppression of pathological AT1R activation. In this study, we examined whether enhancement of ATRAP in the renal distal tubules affects sodium handling and blood pressure regulation in response to high salt (HS) loading, using ATRAP transgenic mice on a salt-sensitive C57BL/6J background. Methods and Results Renal ATRAP transgenic (rATRAP-Tg) mice, which exhibit renal tubule–dominant ATRAP enhancement, and their wild-type littermate C57BL/6J mice on a normal salt diet (0.3% NaCl) at baseline were subjected to dietary HS loading (4% NaCl) for 7 days. In rATRAP-Tg mice, the dietary HS loading–mediated blood pressure elevation was suppressed compared with wild-type mice, despite similar baseline blood pressure. Although renal angiotensin II level was comparable in rATRAP-Tg and wild-type mice with and without HS loading, urinary sodium excretion in response to HS loading was significantly enhanced in the rATRAP-Tg mice. In addition, functional transport activity of the amiloride-sensitive epithelial Na + channel was significantly decreased under saline volume–expanded conditions in rATRAP-Tg mice compared with wild-type mice, without any evident change in epithelial Na + channel protein expression. Plasma membrane AT1R expression in the kidney of rATRAP-Tg mice was decreased compared with wild-type mice. Conclusions These results demonstrated that distal tubule–dominant enhancement of ATRAP inhibits pathological renal sodium reabsorption and blood pressure elevation in response to HS loading. The findings suggest that ATRAP-mediated modulation of sodium handling in renal distal tubules could be a target of interest in salt-sensitive blood pressure regulation.

Description: Nature Physics 9, 419 (2013). doi:10.1038/nphys2642 Authors: F. Kagawa, T. Sato, K. Miyagawa, K. Kanoda, Y. Tokura, K. Kobayashi, R. Kumai & Y. Murakami Geometrically frustrated spin systems often do not exhibit long-range magnetic ordering, resulting in either quantum-mechanically disordered states, such as quantum spin liquids, or classically disordered states, such as spin ices or spin glasses. Geometric frustration may play a similar role in charge ordering, potentially leading to unconventional electronic states without long-range order; however, there are no previous experimental demonstrations of this phenomenon. Here, we show that a charge-cluster glass evolves on cooling in the absence of long-range charge ordering for an organic conductor with a triangular lattice. A combination of time-resolved transport measurements and X-ray diffraction reveals that the charge-liquid phase has two-dimensional charge clusters that fluctuate extremely slowly (〈10–100 Hz) and heterogeneously. On further cooling, the cluster dynamics freezes, and a charge-cluster glass is formed. Surprisingly, these observations correspond to recent ideas regarding the structural glass formation of supercooled liquids. Glassy behaviour has often been found in transition-metal oxides, but only under the influence of randomly located dopants. As organic conductors are very clean systems, the present glassy behaviour is probably conceptually different.