Impaired diluting capacity of the thick ascending limb during loop bicarbonate and nitrate perfusion in vivo

Previous whole animal studies have indicated that when nitrate or bicarbonate is substituted for chloride, renal concentrating defects can be demonstrated. It has been proposed that function of the "distal nephron" or thick ascending limb may be impaired when chloride is replaced by other anions. To examine this proposal, microstop-flow experiments were performed in rats in which loops were perfused with solutions containing 110 mM NaCl, NaHCO3, or NaNO3. Solute reabsorption by the thick ascending limb was assessed by measuring the minimum conductivity of fluid emerging from the loop following intervals of stop-flow. Thick ascending limb solute transport was impaired in loops perfused with HCO3 or NO3 evidenced by the marked increase in solute remaining in the loop after 60 s of stop-flow. The calculated corresponding sodium concentrations were in the range of 17-24 mM Na for the NaCl perfusion, 57-88 mM Na for the NaHCO3 perfusion, and 57-69 mM Na for the NaNO3 perfusion. Clearly, the minimum concentration achieved with NaCl was approximately one-third of that reached with the nitrate or bicarbonate solutions. These results indicate that when chloride-poor solutions reach the thick ascending limb, an important impairment of diluting capacity is demonstrable in vivo in the rat. The present studies, therefore, provide an important link between recent information regarding the mechanism of NaCl transport in the thick ascending limb and older whole animal studies suggesting an important role for distal chloride delivery in urine concentration.