Bidiville J, Roch-Ramel F
J Pharmacol Exp Ther. 1986 May;237(2):636-43.
The excretion of [14C]- or [35S]furosemide and [3H]-p-aminohippurate (PAH) injected within 4 min into the left renal artery of rabbits was measured under brisk mannitol diuresis. The estimated rate of furosemide secretion during the first pass through the left kidney was lower than that of PAH when neither of the two transport processes were saturated: 7.9 and 12.9% of the total amounts injected were secreted per minute, respectively. Different competitive inhibitors were injected i.v. Probenecid (50 mg/kg) inhibited furosemide and PAH secretion by 95 and 80%, respectively. Pyrazinoate at plasma concentrations of 3 to 5 mM had no effect on either anion. Indomethacin (10 mg/kg) depressed furosemide secretion by 24% but had no effect on PAH secretion. PAH at a concentration of 9 to 17 mM in plasma depressed furosemide secretion by only 44 to 66%. Furosemide did not inhibit PAH secretion when infused into the left renal artery at a rate 5000 times higher than PAH. It was concluded that furosemide is secreted partly by the transport system secreting PAH, for which it had only a low affinity, and partly by a transport system for which indomethacin had some affinity. This latter transport system, in turn, differs from that secreting pyrazinoate. The furosemide-induced natriuresis, in both kidneys, was proportional to the urinary excretion rate of furosemide until the fractional excretion of Na+ reached an apparent maximum of 20 to 30%.
在甘露醇强力利尿的情况下，测定了在4分钟内注入兔左肾动脉的[14C] - 或[35S] - 速尿以及[3H] - 对氨基马尿酸（PAH）的排泄情况。当两个转运过程均未饱和时，左肾首次通过时速尿的估计分泌速率低于PAH：每分钟分泌的量分别占注入总量的7.9%和12.9%。静脉注射不同的竞争性抑制剂。丙磺舒（50mg/kg）分别抑制速尿和PAH分泌95%和80%。血浆浓度为3至5mM的吡嗪酸盐对两种阴离子均无影响。消炎痛（10mg/kg）使速尿分泌减少24%，但对PAH分泌无影响。血浆中浓度为9至17mM的PAH仅使速尿分泌减少44%至66%。当以比PAH高5000倍的速率注入左肾动脉时，速尿不抑制PAH分泌。得出的结论是，速尿部分通过分泌PAH的转运系统分泌，速尿对该系统的亲和力较低，部分通过消炎痛具有一定亲和力的转运系统分泌。后一种转运系统又不同于分泌吡嗪酸盐的转运系统。速尿诱导的双侧肾脏利钠作用与速尿的尿排泄率成正比，直到Na +的分数排泄达到明显最大值20%至30%。
