Abstract 421: Dehydration Upregulates the Full-length (Pro)renin Receptor Expression in the Kidney of Wistar-Kyoto Rats and Spontaneously Hypertensive Rats

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Abstract

(Pro)renin receptor ((P)RR) was newly identified as a member of the renin-angiotensin system (RAS). (P)RR exists in two forms; full-length form (f(P)RR) and soluble form (s(P)RR). The truncated hydrophilic s(P)RR is generated by furin cleavage in the trans-Golgi network and is secreted into the extracellular space. Compared with Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) demonstrated low urine concentration ability and resistance to vasopressin in a state of dehydration (DH). RAS system contributes to the regulation of body fluid balance, but roles of (P)RR in a state of dehydration (DH) are not clarified. The purpose of this study was to examine the effects of DH on the (P)RR expression in the kidney of WKY and SHR. Twelve week-old, male WKY and SHR were randomly divided into two groups (n=5 in each group); control and DH groups. DH was induced by water restriction for 72 hours in metabolic cage. After 72 hours, rats were killed, and (P)RR protein levels in plasma, urine and kidney were examined by using Western blot. (P)RR mRNA levels were examined by using competitive RT-PCR methods. In addition, furin protein levels were also investigated. DH increased urine osmolarity in WKY and SHR (4090±451 and 3796±429 mOsm/kg). DH significantly decreased the s(P)RR levels in the plasma of WKY and SHR (0.3- and 0.7-fold, P<0.01), but significantly increased in the urine of these rats (1.5- and 3.3-fold, P<0.05). DH significantly increased the f(P)RR levels in the renal homogenates, microsome fraction, and cytosol fraction of WKY and SHR (WKY: 2.3-, 3.0-, and 22.9-fold, SHR: 2.3-, 2.1-, and 7.9-fold, P<0.01). DH did not change the s(P)RR levels in the renal homogenates and cytosol fraction of these rats. In the kidney, DH did not change (P)RR mRNA levels in WKY, but significantly increased them in SHR (2.7-fold, P<0.05). DH significantly decreased furin protein levels in WKY (0.7-fold, P<0.05), but did not change them in SHR. These results indicate that DH upregulates the f(P)RR expression in the kidney of WKY and SHR. The DH-upregulated f(P)RR expression might be mediated through the decrease of furin levels in WKY and increase of (P)RR mRNA levels in SHR.

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