Datar S, McCauley F A, Wilson T W
Prostaglandins. 1987 Feb;33(2):275-85. doi: 10.1016/0090-6980(87)90012-8.
Furosemide increases the synthesis of two major renal eicosanoids, prostacyclin (PGI2) and thromboxane A2 (TXA2), by stimulating the release of arachidonic acid which in turn is metabolized to PGG2/PGH2, then to PGI2 and TXA2. PGI2 may mediate, in part, the early increment in plasma renin activity (PRA) after furosemide. We hypothesized that thromboxane synthetase inhibition should direct prostaglandin endoperoxide metabolism toward PGI2, thereby enhancing the effects of furosemide on renin release. Furosemide (2.0 mg . kg-1 i.v.) was injected into Sprague-Dawley rats pretreated either with vehicle or with U-63,557A (a thromboxane synthetase inhibitor, 2 mg/kg-1 followed by 2 mg/kg-1 X hr-1). Urinary 6ketoPGF1 alpha and thromboxane B2 (TXB2), reflecting renal synthesis of PGI2 and TXA2, as well as PRA and serum TXB2, were measured. Serum TXB2 was reduced by 96% after U-63,557A. U-63,557A did not affect the basal PRA. Furosemide increased PRA in both vehicle and U63,557A treated rats. However, the PRA-increment at 10, 20 and 40 min following furosemide administration was greater in U-63,557A-treated rats than in vehicle-treated rats and urine 6ketoPGF1 alpha excretion rates were increased. These effects of thromboxane synthesis inhibition are consistent with a redirection of renal PG synthesis toward PGI2 and further suggest that such redirection can be physiologically relevant.
呋塞米通过刺激花生四烯酸的释放来增加两种主要的肾类二十烷酸——前列环素（PGI2）和血栓素A2（TXA2）的合成，花生四烯酸进而代谢为PGG2/PGH2，然后再代谢为PGI2和TXA2。PGI2可能部分介导了呋塞米给药后血浆肾素活性（PRA）的早期升高。我们推测，抑制血栓素合成酶应使前列腺素内过氧化物代谢导向PGI2，从而增强呋塞米对肾素释放的作用。将呋塞米（2.0毫克·千克-1静脉注射）注入预先用赋形剂或U-63557A（一种血栓素合成酶抑制剂，2毫克/千克-1，随后2毫克/千克-1×小时-1）处理的Sprague-Dawley大鼠体内。测量反映肾PGI2和TXA2合成的尿6-酮-PGF1α和血栓素B2（TXB2），以及PRA和血清TXB2。U-63557A处理后血清TXB2降低了96%。U-63557A不影响基础PRA。呋塞米使赋形剂处理组和U-63557A处理组大鼠的PRA均升高。然而，在呋塞米给药后10、20和40分钟时，U-63557A处理组大鼠的PRA升高幅度大于赋形剂处理组大鼠，且尿6-酮-PGF1α排泄率增加。抑制血栓素合成的这些作用与肾PG合成向PGI2的重定向一致，并进一步表明这种重定向可能具有生理相关性。
