Afferent renal denervation or oral amiloride significantly reduced chlorthalidone-induced saline intake in rats (P<0.01 for males, P<0.001 for females).
Renal interoception via ENaC-mediated sodium reabsorption drives salt consumption behavior, which can be attenuated by renal denervation or amiloride.
p-value: p=<0.01
Global sodium intake continues to exceed recommended limits, contributing to the widespread prevalence of hypertension and cardiovascular disease. Our laboratory has recently identified a novel interoceptive role for the kidney in the regulation of sodium intake. We demonstrated that ablation of the sensory renal nerves caused a selective reduction in saline intake in the DOCA rat model of primary aldosteronism. In the current study, we tested the hypothesis that ENaC-mediated sodium reabsorption in the kidney causes an increase in sensory afferent renal nerve activity, which results in a behavioral drive to consume salt. Two bottle preference tests were performed in which male (M) and female (F) Sprague Dawley rats were offered free access to both deionized water (dH 2 O) and hypertonic saline (1.8% NaCl). This enabled the separation of thirst and salt preference. Rats were studied over 14 days. Oral chlorthalidone (CTD) was used to inhibit NCC and increase both sodium delivery to the collecting duct and ENaC activity. Oral amiloride (Ami) was used to inhibit ENaC. Afferent renal denervation (ARDN) was performed bilaterally (33 mM periaxonal capsaicin). Five groups of rats were studied: Vehicle (peanut butter, p.o; n=9M, 6F), CTD (5mg/kg, p.o; n=9M, 6F), CTD-ARDN (n=6M, 7F), CTD-Ami (10mg/kg p.o; n=8M, 6F), and CTD-ARDN-Ami (6M, 6F). Resting afferent renal nerve activity (ARNA) was assessed in additional groups of Vehicle (5M, 5F), CTD (6M, 5F) and CTD-Ami (6M, 6F) rats. Temporal data were analyzed using a linear mixed model and a Tukey post hoc test. Terminal data was analyzed using a one-way ANOVA and Tukey test. In M and F rats, CTD caused a significant increase in saline intake relative to vehicle controls (CTD vs. Vehicle, M: P0.05). ARDN, which removes sensory input from the kidney, prevented the increased saline intake (CTD vs. CTD-ARDN M: P0.05 for all comparisons). Relative to vehicles, CTD caused a significant increase in ARNA in male but not female rats (CTD vs. Vehicle, M: P< 0.01, F: P=0.391). In both sexes, resting ARNA was significantly lower in rats treated with CTD-Ami compared with CTD alone (CTD vs. CTD-Ami. M+F: P< 0.05). In ongoing studies, we are performing lick microstructure analysis to assess whether the reduced salt intake following ARDN is the result of reduced palatability and/motivation. Our data unveils an interoceptive role for the kidney in the regulation of salt intake. We propose that both renal denervation and oral amiloride may be novel ways to modulate salt intake, particularly in high-risk patients. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Anidu et al. (Fri,) conducted a other in Salt consumption (n=102). Chlorthalidone, Afferent renal denervation, and Amiloride vs. Vehicle was evaluated on Saline intake (p=<0.01). Afferent renal denervation or oral amiloride significantly reduced chlorthalidone-induced saline intake in rats (P<0.01 for males, P<0.001 for females).