Sodium appetite is enhanced in 5/6 nephrectomized rat by high-sodium diet via increased levels of angiotensin II in the subfornical organ.

Intracerebral renin-angiotensin system (RAS) activation in the forebrain nuclei, such as the subfornical organ (SFO) is among the important factors that increase sodium appetite in rats. Although an increased sodium appetite in congestive heart failure and spontaneously hypertensive rats was reported previously, few reports have shown an increased sodium appetite in chronic kidney disease (CKD) model rats, for which salt restriction is important. Here, we aimed to verify whether CKD model rats show increased sodium appetite and if therapeutic intervention reducing sodium appetite by suppressing the intracerebral RAS is possible. In this study, 5/6 nephrectomized (5/6Nx) and control rats were fed a high-salt (4% NaCl) or low-salt (0.04% NaCl) diet. Angiotensin II (AngII) levels in kidney and the SFO, renal injury, and sodium appetite were evaluated after 2 weeks of salt loading. The 5/6Nx high-salt diet (Nx-HS) group was further divided into subgroups receiving continuous intracerebroventricular (ICV) administration of the angiotensin II type 1 receptor (AT1R) antagonist ZD 7155 or saline. Compared with the control rats, the 5/6Nx rats exhibited significantly increased levels of AngII in kidney and the SFO, accompanied by elevated blood pressure and worsened renal injury, especially in the Nx-HS group. In the Nx-HS group, an increased sodium appetite was observed that was attenuated by the ICV administration of ZD 7155 but not by saline. In conclusion, a high-salt diet enhanced the sodium appetite of 5/6Nx rats via increased levels of AngII in the SFO, which was attenuated by continuous ICV administration of an AT1R antagonist.