Diz D I, Kauker M L
Arch Int Pharmacodyn Ther. 1980 Feb;243(2):321-30.
The effects of indomethacin, a PG synthesis inhibitor, on the renal hemodynamic and diuretic responses to indanone were evaluated in 10 rats and 12 dogs. In anaesthetized rats, 50 mg/kg of indanone, an indanyloxyacetic acid diuretic, increased water excretion 20--30 times, sodium excretion 80--100 times, and potassium excretion 4 times, without marked changes in GFR and BP. Indomethacin pretreatment, 2 mg/kg, did not significantly reduce these responses. In vehicle pretreated dogs, urine flow, and sodium and potassium excretions increased 9,7 and 2 fold, respectively, after 4 mg/kg indanone. These responses were significantly diminished in dogs pretreated with 4 mg/kg indomethacin. Mean RBF was reduced 17% (P less than 0.02) after 10 min of indanone infusion (0.2 mg/kg/min). Indomethacin failed to alter this effect, suggesting the action of indanone differs from that of furosemide and ethacrynic acid, agents know to cause PG mediated renal vasodilation. The cyclooxygenase inhibitor did inhibit the diuretic response to indanone in these dogs. The dissimilar renal excretory response in the two species may reflect a more effective blockade by indomethacin of the tubular secretion of indanone in dogs than in rats. Alternatively, PGs may have different renal effects in the two species, or cyclooxygenase was inhibited to a greater extent in dogs than in rats.
在10只大鼠和12只狗身上评估了PG合成抑制剂吲哚美辛对茚满二酮的肾血流动力学和利尿反应的影响。在麻醉的大鼠中，50mg/kg的茚满二酮（一种茚满氧基乙酸利尿剂）使水排泄增加20 - 30倍，钠排泄增加80 - 100倍，钾排泄增加4倍，而肾小球滤过率（GFR）和血压（BP）无明显变化。2mg/kg的吲哚美辛预处理并未显著降低这些反应。在用赋形剂预处理的狗中，4mg/kg茚满二酮给药后，尿流量、钠和钾排泄分别增加了9倍、7倍和2倍。在用4mg/kg吲哚美辛预处理的狗中，这些反应显著减弱。茚满二酮输注10分钟（0.2mg/kg/min）后，平均肾血流量（RBF）降低了17%（P<0.02）。吲哚美辛未能改变这种作用，这表明茚满二酮的作用不同于速尿和依他尼酸，已知这两种药物可引起PG介导的肾血管舒张。环氧化酶抑制剂确实抑制了这些狗对茚满二酮的利尿反应。两种物种不同的肾排泄反应可能反映出吲哚美辛对狗肾小管分泌茚满二酮的阻断作用比对大鼠更有效。或者，PG在两种物种中可能具有不同的肾脏作用，或者环氧化酶在狗中比在大鼠中受到更大程度的抑制。
