PROSTAGLANDIN-INDEPEDENT PROTECTION BY FUROSEMIDE FROM OLIGURIC ISCHEMIC RENAL-FAILURE IN CONSCIOUS RATS
PROSTAGLANDIN-INDEPEDENT PROTECTION BY FUROSEMIDE FROM OLIGURIC ISCHEMIC RENAL-FAILURE IN CONSCIOUS RATS
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DOI：
10.1038/ki.1980.53
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发表时间：
1980-01-01
影响因子：
19.6
通讯作者：
DUSING, R
中科院分区：
文献类型：
--
作者：
KRAMER, HJ;SCHUURMANN, J;DUSING, R
38只清醒大鼠分为7组，左肾动脉完全闭塞1小时，而对侧肾脏保持完整，诱导急性单侧缺血性肾功能衰竭。缺血后144小时监测左肾排泄功能，发现典型的少尿肾功能衰竭过程，少尿持续48小时以上。肾动脉闭塞解除后，尿渗透压和钠浓度变为血浆等渗，缺血后第6天接近对照值。在9只大鼠中，在肾动脉闭塞之前（6 μ g/min/100 g体重）和之后（12 μ g/min/100 g体重）静脉输注呋塞米保护缺血性肾免于少尿，内源性肌酐清除率为0.42 ± 0.01。0.11 ml/min/g肾重量。肾小管吸收钠和水至少部分保存缺血后36小时，当输液呋塞米停止。袢利尿剂显著增加肾动脉阻断前后尿前列腺素E2（PG E2）的排泄量（P < 0.01），缺血后5 h，缺血肾PGE 2的排泄量显著高于完整肾（P < 0.05）。在6只动物中给予吲哚美辛（1 mg/100 g体重）显著抑制对照PGE 2排泄（P < 0.05）和缺血前后呋塞米诱导的尿PG排泄增加，但在该实验模型中没有改变利尿剂的保护作用。PG合成的抑制减少了对侧完整肾脏的尿流率和Na和K排泄，几乎完全阻止了肌酐清除率的代偿性升高。肾内PG系统以外的机制必须介导速尿在急性缺血性肾功能衰竭中的保护作用。
In 38 conscious rats divided into 7 groups, acute unilateral ischemic renal failure was induced by 1 h of complete occlusion of the left renal artery while the contralateral kidney remained intact. Renal excretory function of the left kidney was monitored up to 144 h after ischemia and revealed a typical course of oliguric renal failure with oligoanuria persisting for more than 48 h. Urinary osmolality and Na concentration became plasma isotonic after release of renal artery occlusion and approximated control values on day 6 after ischemia. In 9 rats, the i.v. infusion of furosemide before (6 .mu.g/min per 100 g body wt) and after (12 .mu.g/min per 100 g body wt) renal artery occlusion protected the ischemic kidney from oligoanuria with endogenous creatinine clearance of 0.42 .+-. 0.11 ml/min per g kidney wt 5 h after ischemia. Tubular absorption of Na and water was at least partially preserved 36 h after ischemia when infusion of furosemide was stopped. The loop diuretic significantly (P < 0.01) increased total urinary prostaglandin (PG) E2 excretion before and after renal artery occlusion; and 5 h after ischemia, PGE2 excretion from the ischemic kidney significantly exceeded that from the intact kidney (P < 0.05). Indomethacin (1 mg/100 g body wt) administered in 6 animals markedly suppressed control PGE2 excretion (P < 0.05) and the furosemide-induced rise in urinary PG excretion before and after ischemia but did not modify the protective effect of the diuretic in this experimental model. Inhibition of PG synthesis reduced urinary flow rate and Na and K excretion of the contralateral intact kidney and almost completely prevented its compensatory rise in creatinine clearance. Mechanisms other than the intrarenal PG system must mediate the protective effects of furosemide in acute ischemic renal failure.