Water Deprivation Increases (Pro)renin Receptor Levels in the Kidney and Decreases Plasma Concentrations of Soluble (Pro)renin Receptor

Water Deprivation Increases (Pro)renin Receptor Levels in the Kidney and Decreases Plasma Concentrations of Soluble (Pro)renin Receptor

YUMA TAMURA,¹ NOBUYOSHI MORI,¹ BIN XU1, TAKAHIRO NAKAMURA,¹ SEIKO YAMAKOSHI,¹ TAKUO HIROSE,² OSAMU ITO,¹ KAZUHITO TOTSUNE,³ KAZUHIRO TAKAHASHI⁴ and MASAHIRO KOHZUKI¹

¹Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
²Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
³Department of Social Welfare, Faculty of Synthetic Welfare, Tohoku Fukushi University, Sendai, Miyagi, Japan
⁴Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Water deprivation activates the renin-angiotensin system. We have hypothesized that the renal expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, could be changed under dehydration. Moreover, plasma levels of soluble (P)RR (s(P)RR) comprising of the extracellular domain of (P)RR may reflect the renal (P)RR expression. In the present study, we therefore aimed to clarify changes of plasma s(P)RR concentrations and kidney tissue (P)RR levels using rats with dehydration. Male Wister-Kyoto rats were divided into two groups; dehydrated (DH) rats deprived of water for 72 hours with free access to food, and control rats. Plasma s(P)RR concentrations measured by enzyme-linked immunosorbent assay were significantly lower in DH rats (6.94 ± 2.08 ng/mL, mean ± SD, n = 5) than in control (12.54 ± 2.00 ng/mL, n = 5) (p < 0.05). Western blot analysis confirmed lower expression levels of s(P)RR in plasma in DH rats than in control. By contrast, western blot analysis showed higher levels of full-length (P)RR and lower levels of furin (an enzyme responsible for generation of s(P)RR from full-length (P)RR) in the kidney tissues obtained from DH rats compared to control. There was no significant difference in the renal (P)RR mRNA levels between DH rats and control. These findings suggest that water deprivation may elevate the renal full-length (P)RR levels via reducing the expression of furin. Increased full-length (P)RR may contribute to the up-regulation of the renal renin-angiotensin system and the production of concentrated urine under dehydration.

keywords —— dehydration; prorenin; receptor; renin; water deprivation

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Tohoku J. Exp. Med., 2016, 239, 185-192

Correspondence: Nobuyoshi Mori, Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: nobuyosi@m.tohoku.ac.jp