Katayama S, Attallah A A, Stahl R A, Bloch D L, Lee J B
Am J Physiol. 1984 Oct;247(4 Pt 2):F555-61. doi: 10.1152/ajprenal.1984.247.4.F555.
Studies were conducted to investigate the interaction of renal prostaglandin E2 (PGE2) production and the renin-angiotensin system in the mechanism of furosemide-induced natriuresis. In conscious rabbits with permanent urinary bladder cannulation, furosemide in vivo (10 mg/kg) increased urinary water, sodium, and PGE2 excretion and plasma renin activity (PRA) over 50 min. Furosemide administered in vivo enhanced renal papillary but not cortical in vitro PGE2 biosynthesis. Prior administration of indomethacin at 2 mg/kg augmented the saluretic effect of furosemide, decreased its effect on UPGE2 V, abolished the rise in PRA, and reduced cortical but not papillary PGE2 biosynthesis. However, at 10 mg/kg, indomethacin reduced the saluretic effect of furosemide and eliminated the increase in UPGE2 V with continued suppression of PRA. Direct addition of furosemide in vitro to the incubation medium (10(-5) and 10(-3) M) markedly augmented papillary PGE2 synthesis. It is concluded that furosemide stimulates renal papillary PGE2 biosynthesis directly without mediation by angiotensin II, resulting in an increase in UPGE2 V, and the enhanced or inhibitory effect of indomethacin on furosemide-induced natriuresis is dose related and dependent on the degree of PGE2 synthesis inhibition in the presence of suppressed PRA, which occurred at all doses studied.
开展了多项研究，以探讨肾前列腺素E2（PGE2）生成与肾素-血管紧张素系统在速尿诱导利钠机制中的相互作用。在永久性膀胱插管的清醒兔中，速尿体内给药（10mg/kg）在50分钟内增加了尿水、钠和PGE2排泄以及血浆肾素活性（PRA）。速尿体内给药增强了肾乳头而非皮质的体外PGE2生物合成。预先给予2mg/kg的吲哚美辛可增强速尿的利尿作用，降低其对尿PGE2排泄量（UPGE2 V）的作用，消除PRA的升高，并减少皮质而非肾乳头的PGE2生物合成。然而，给予10mg/kg时，吲哚美辛降低了速尿的利尿作用，并消除了UPGE2 V的增加，同时持续抑制PRA。在体外将速尿直接添加到孵育培养基中（10^(-5)和10^(-3)M）可显著增强肾乳头PGE2合成。得出的结论是，速尿直接刺激肾乳头PGE2生物合成，无需血管紧张素II介导，导致UPGE2 V增加，吲哚美辛对速尿诱导利钠的增强或抑制作用与剂量相关，并取决于在PRA受抑制情况下PGE2合成的抑制程度，在所研究的所有剂量下均会出现这种情况。
