Hydrochlorothiazide causes sodium sensitization in rats

Abstract

Sodium is an important ion for physiological functions, especially the maintenance of membrane potentials and osmotic gradients. The balance of sodium within the body is regulated both through sodium intake (primarily through food and drink), and output (in urine, saliva, and other bodily fluids). Previous studies have shown that repeated acute sodium depletion with the diuretic/natriuretic drug furosemide causes behavioral sensitization as indicated by the enhanced intake of sodium containing solutions (i.e., salt appetite) in response to the induced deficits. In humans, the diuretic compound hydrochlorothiazide (HCZ) is commonly used to treat hypertension. The present study was designed to examine if HCZ causes behavioral sensitization in the absence of a sodium deficiency in order to determine the mechanisms through which salt appetite is enhanced. Sprague‐Dawley rats maintained on standard‐sodium chow with access to 0.3 M NaCl and distilled water were injected with either vehicle or 2.5 mg/kg HCZ for 2 weeks. Ad lib intake of 0.3 M NaCl was significantly increased during HCZ treatment and importantly remained elevated beyond the washout period. In this paradigm, rats never experienced severe sodium deficiency, yet 0.3 M NaCl intake was increased even under ad lib conditions. These data have implications for humans treated with HCZ and directed to consume a low sodium diet. (Support: NIH HL14388 & HL007121).