Gender and obesity influence sodium intake and fluid regulation in Zucker rats following repeated sodium depletions

The Zucker obese rat is an important model for the metabolic syndrome, which includes renal disease and salt-sensitive hypertension, suggesting abnormalities of body fluid regulation. Here, in Zucker rats, lean and obese, and of both sexes, we compared 48 h of sodium intake and fluid regulation responses with repeated depletions with furosemide to repeated control saline injections. Increased urine volume excretion was observed after each furosemide administration for the 4 groups and obese rats excreted more than the leans on the control days. Male obese rats did not excrete sodium nor increase intake of 2% NaCl following the first furosemide administration, whereas the other 3 groups did. Subsequent depletions increased 2% NaCl consumption and urinary sodium excretion in all groups. Males excreted more sodium in their urine than the females on the control days. Females showed an increase in 2% NaCl intake on control days. Water intake increased in the female leans after each depletion, increased in the males after the 2nd and 3rd depletion and increased in the obese females only after the 2nd depletion. These findings show clearly that there are gender- and weight-related differences in the response of Zucker rats to furosemide-induced depletion. However, the main differences occurred with the first depletion. With repeated depletions the rats adjusted sodium and fluid intake and excretion so that differences due to gender and body weight tended to disappear. Our findings caution against drawing conclusions about differences due to gender and body weight based on single treatments.