Department of Anesthesia, Division of Nephrology, University of Toronto, St. Michael's Hospital, Keenan Research Centre in the Li Ka Shing Knowledge Institute, Toronto, Ont., Canada.
Nephron Physiol. 2012;122(1-2):7-12. doi: 10.1159/000346741. Epub 2013 Mar 15.
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.
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).
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.
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.
背景/目的：由于呋塞米（FS）抑制髓质升支厚段（mTAL）中的主动 Na(+) 重吸收，因此它可能会降低肾脏外髓质深处低氧供应期间的工作。本研究旨在证明可能存在一个 FS 剂量可以降低其代谢工作，同时防止镁（Mg(2+)）的过度丢失。Mg(2+) 很重要，因为执行工作所需的 ATP 必须与之结合 Mg(2+)。
向大鼠腹膜内注射一系列剂量的 FS。测量的结果是尿流量和 mTAL 的功能参数（即尿和肾乳头渗透压以及尿中 Na(+)、Cl(-)、K(+) 和 Mg(2+) 的排泄，以及血清中 Mg(2+) 的浓度）。
FS 起始剂量为 2.4 mg/kg 时，尿流量明显增加。肾乳头渗透压在≥0.4 mg FS/kg 时降低，起始剂量为 1.6 mg FS/kg 时，出现可检测到的大量钠排泄。在后一个剂量下，尿中 Mg(2+) 的排泄显著增加。
在大鼠中，非利尿剂量的 FS 可能会降低 mTAL 的工作。mTAL 工作减少的最早指标似乎是尿液渗透压降低，而不是尿流量增加。应避免使用更高剂量的 FS，因为它们会诱导高 Mg(2+) 排泄率，从而导致体内这种必需电解质的消耗。
