Non-Natriuretic Doses of Furosemide: Potential Use for Decreasing the Workload of the Renal Outer Medulla with Minimal Magnesium Wasting in the Rat

Abstract

Background/Aims: Since furosemide (FS) inhibits active Na⁺ reabsorption by medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease its work during periods of low O₂ supply to deep in the renal outer medulla. This study was designed to demonstrate that there may be a dose of FS would reduce its metabolic work while preventing the excessive loss of magnesium (Mg²⁺). Mg²⁺ is important because the ATP needed to perform work must have bound Mg²⁺ to it. Methods: Rats were injected intraperitoneally with a range of doses of FS. The measured outcomes were urine flow rate and parameters of functions of the mTAL (i.e. urine and renal papillary osmolality and urinary excretion of Na⁺, Cl^-, K⁺ and Mg²⁺, and concentrations of Mg²⁺ in serum). Results: The urine flow rate increased significantly starting at 2.4 mg FS/kg. The renal papillary osmolality decreased at ≥0.4 mg FS/kg, and the large detectable natriuresis started at 1.6 mg FS/kg. At this latter dose, the urinary excretion of Mg²⁺ rose significantly. Conclusion: In rats, the non-natriuretic dose of FS may reduce the work of the mTAL. The earliest indicator of reduced work in the mTAL appears to be a decrease in urine osmolality rather than a rise in urine flow rate. Higher doses of FS should be avoided, as they induce high rates of Mg²⁺ excretion, which can deplete the body of this essential electrolyte.