Sreenivasan V, Walker B, Krasney J, Mookerjee B, Venuto R
Hypertension. 1981 Jan-Feb;3(1):59-66. doi: 10.1161/01.hyp.3.1.59.
The renal effects of two structurally dissimilar inhibitors of prostaglandin synthesis (Meclofenamate and RO-20-5720) were studied in conscious, chronically instrumented dogs during mild volume expansion and during a constant infusion of furosemide. When either inhibitor was administered following volume expansion, urinary excretion of PGE2 and urine flow rate were reduced by more than 50%. In contrast, renal plasma flow fell by less than 10% while glomerular filtration rate, sodium excretion, and plasma renin activity (PRA) were unchanged. In separate studies, infusion of furosemide increased renal plasma flow, urine flow rate, sodium excretion, PRA, and urinary excretion of PGE2, while glomerular filtration rate decreased. Administration of inhibitors of prostaglandin synthesis during constant infusion of furosemide reduced the urinary excretion of PGE2 to control levels, as renal plasma flow and glomerular filtration rate fell below control level. Despite these hemodynamic alterations, the furosemide-induced diuresis and increase in PRA were only partly attenuated by prostaglandin inhibition. It is concluded that in conscious dogs, intrarenal prostaglandins modulate urine flow rate during mild volume expansion and play a major role in mediating the renal hemodynamic effects of furosemide.
在轻度容量扩张期间以及持续输注速尿的过程中，对清醒且长期植入仪器的犬类研究了两种结构不同的前列腺素合成抑制剂（甲氯芬那酸和RO-20-5720）对肾脏的影响。在容量扩张后给予任何一种抑制剂时，PGE2的尿排泄量和尿流率均降低了50%以上。相比之下，肾血浆流量下降不到10%，而肾小球滤过率、钠排泄和血浆肾素活性（PRA）均未改变。在单独的研究中，输注速尿可增加肾血浆流量、尿流率、钠排泄、PRA和PGE2的尿排泄量，而肾小球滤过率降低。在持续输注速尿期间给予前列腺素合成抑制剂，可使PGE2的尿排泄量降至对照水平，同时肾血浆流量和肾小球滤过率降至对照水平以下。尽管存在这些血流动力学改变，但前列腺素抑制仅部分减弱了速尿诱导的利尿作用和PRA的增加。结论是，在清醒犬类中，肾内前列腺素在轻度容量扩张期间调节尿流率，并在介导速尿的肾脏血流动力学效应中起主要作用。
