Abstract: TH-OR60
Chlorthalidone-Induced Salt Appetite Is Prevented by Afferent Renal Denervation
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Back to the Basics
October 24, 2024 | Location: Room 4, Convention Center
Abstract Time: 05:20 PM - 05:30 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Anidu, Babatunde Shuaib, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Costa Veiga, Amanda, University of Minnesota Twin Cities, Minneapolis, United States
- Ross, Jaryd, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Almutlaq, Rawan N., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Dayton, Alexander R., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Evans, Louise Christine, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
Background
Excessive sodium intake is a significant public health concern, with the average American consuming approximately 3,400 mg daily, ~1g more than the American Heart Associations’ recommended daily maximum. Reducing sodium intake is one of the most cost-effective ways to reduce death from non-communicable diseases and improve health outcomes.
Our lab has shown that afferent renal denervation (ARDN) reduces sodium intake in male hypertensive DOCA-salt rats. We hypothesize that when the body needs to conserve sodium, afferent renal nerves are activated in response to increased sodium reabsorption in the collecting duct and this stimulates salt intake. To test this, we used chlorthalidone (CTD) to inhibit the sodium-chloride cotransporter (NCC) in the distal convoluted tubule. This increases sodium delivery to the collecting duct. We examined whether CTD causes increased sodium intake and whether this is prevented by ARDN.
Methods
Male Sprague-Dawley rats aged 10-14 weeks were divided into three groups: vehicle (peanut butter, p.o, n=9), CTD (5mg/kg, p.o, n=8), and CTD-ARDN (n=6). The CTD-ARDN group underwent bilateral ARDN (periaxonal capsaicin, 33mM). The other two groups underwent sham surgery. Telemeter catheters were inserted in the femoral artery of all rats for the assessment of mean arterial pressure (MAP). After surgical recovery, all rats had ad libitum access to a low-salt diet (0.01% NaCl) and deionized water and 1.8% saline for 14 days.
Results
Chronic CTD caused a significant increase in saline intake relative to the vehicle treated rats (p<0.001). This effect was specific for saline, and water intake was not higher in CTD than vehicle rats (p=0.4). ARDN caused a significant reduction in saline (p=0.02) but not water (p=0.5) intake. Neither CTD nor ARDN had a significant effect on MAP. Ongoing studies are evaluating whether CTD increases salt-appetite in female rats, and if this is dependent on afferent renal nerves.
Conclusion
These studies show, for the first time, that inhibition of NCC causes a specific increase in salt appetite which is driven by the activation of the afferent renal nerves. In future studies, we will use the administration of amiloride to evaluate whether this response is dependent on the activation of ENaC.
Funding
- Other NIH Support