Conscious Dahl Salt‐Sensitive Rats Excrete a Volume Load Slower than Sprague Dawley Rats Due to a Defect in Thick Ascending Limb Transport

Abstract

Dahl salt‐sensitive rats have an impaired excretory ability when compared to the parent Sprague‐Dawley strain due to a renal defect. However, nearly all studies have been performed in anesthetized animals raising the possibility that differences between strains are the result of the anesthesia. Although in vitro data indicate that at least part of the defect is due to enhanced NaCl reabsorption by thick ascending limbs in the salt‐sensitive strain, this has not been demonstrated in conscious, whole‐animal experiments. We hypothesized that conscious Dahl salt‐sensitive rats have an impaired ability to excrete an acute volume load to abnormal thick ascending limb NaCl reabsorption. To test our hypothesis, Dahl salt‐sensitive and Sprague‐Dawley rats were placed in metabolic cages and trained to drink their daily water intake in just two hours creating a modest volume load. On the day of the experiment, rats were given a 1% sucrose solution for just one hour with and without furosemide, an inhibitor of thick ascending limb NaCl reabsorption. Urine was collected every 30 minutes for 3 hours. At 60, 90, 120 and 150 min, cumulative urinary volume was lower in salt‐sensitive compared to Sprague‐Dawley rats (60 min: 1±0.3 vs. 7±1, p<0.05; 90 min: 7±1 vs. 18±2, p<0.01; 120 min: 14±1 vs. 24±1, p<0.01; 18±1 vs. 26±2, p<0.05). By 180 min, cumulative urinary volumes were no longer different. Cumulative urinary Na excretion, expressed as percent of total urinary Na excretion, was also lower in Dahl salt‐sensitive rats (60 min: 43±6 vs. 65±6, p<0.05; 90 min: 74±4 vs. 89±2, p<0.01; 120 min: 87±4 vs. 97±1, p<0.01). Furosemide increased dramatically both cumulative urinary volume and urinary Na excretion, and eliminated the differences between strains. We conclude that conscious Dahl salt‐sensitive rats have a defect in thick ascending limb NaCl reabsorption that impairs their ability to excrete an acute volume load. This defect likely contributes to the salt‐sensitivity of blood pressure in this strain.Support or Funding InformationThis work was supported in part by grants to Jeffrey Garvin from the National Institutes of Health (HL 70985) and to Fara Saez from the American Heart Association (15POST22650010 ).