Sex differences in the regulation of salt appetite in Spontaneously Hypertensive Rats after loss of interoceptive input from the kidney

Abstract

The average American consumes 3,400 mg/day of sodium, 1000mg over the American Heart Association’s recommended maximum daily allowance. Excessive salt intake accelerates the progression of many diseases including hypertension, congestive heart failure, and chronic kidney disease. Reducing sodium intake has beneficial effects on a population level and in at risk patients. In previous studies we have shown that afferent renal nerves are involved in the regulation of sodium intake in DOCA hypertensive rats. Like DOCA hypertensive rats, Spontaneously Hypertensive rats (SHR) are a model with increased salt appetite. Here, we tested the hypothesis that afferent renal nerves regulate sodium intake in SHR. Secondarily, it is well documented that estrogens modulate salt intake. To examine the effect of sex on sodium intake we compared salt-appetite between male and female SHR. Bilateral afferent renal denervation (ARDN) was performed using the periaxonal application of 33mM capsaicin. In sham rats the renal arteries were isolated but not treated. Mean arterial blood pressure (MAP) was assessed using radiotelemetry, with the catheter implanted in the femoral artery. Four groups of rats were studied: male SHR-sham (n=9), female SHR-sham (n=3), male SHR+ARDN (n=8) and female SHR+ARDN (n=4). All rats were given ad libitum access to two bottles, one containing dH2O and the other containing 1.8% NaCl. The bottle position was rotated, and fluid intake was recorded daily for 21-days. ARDN caused a significant reduction in 1.8% intake in female but not male SHR rats (p=0.02, female SHR-sham v female SHR-ARDN, p>0.99 male SHR v male SHR-ARDN). This effect was specific for saline intake, water intake was not altered by ARDN in the female SHR (p=0.3). The female SHR drank more saline than male SHR when normalized to body weight (p=0.04 female SHR-sham v male SHR-sham). MAP was not reduced by ARDN in the male SHR (p=0.39), and ongoing studies are examining MAP in response to ARDN in female SHR. The data presented demonstrate for the first time that ARDN decreases salt appetite in female but not male SHR. We also found that baseline saline intake was higher in female SHR than male SHR. In future studies we will examine the renal mechanisms underlying these sex differences. Together, these data suggest that reduced sodium intake may offer an additional therapeutic benefit of renal denervation in female patients with hypertension and cardiovascular disease. LE is funded by R01HL152166; ACV is funded by FAPESP. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.