Non-natriuretic doses of furosemide: potential use for decreasing the workload of the renal outer medulla with minimal magnesium wasting in the rat.

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 (Mg(2+)). Mg(2+) is important because the ATP needed to perform work must have bound Mg(2+) 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 Mg(2+), and concentrations of Mg(2+) 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 Mg(2+) 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 Mg(2+) excretion, which can deplete the body of this essential electrolyte.