Katayama S, Inaba M, Maruno Y, Omoto A, Itabashi A, Kawazu S, Ishii J
Fourth Department of Medicine, Saitama Medical School, Japan.
Prostaglandins. 1989 Oct;38(4):401-11. doi: 10.1016/0090-6980(89)90123-8.
Since one of the hypotensive mechanisms of angiotensin-converting enzyme inhibitor (ACEI) has been suggested to be mediated through the renal kinin-prostaglandin (PG) axis, the present study was designed to investigate the effect of captopril (C) or enalapril (E) on renal PGE2 excretion or synthesis. Wistar male rats (BW 200-250 g) were given orally captopril at 30 mg/kg/day or enalapril at 10 or 30 mg/kg for one week. Before and after ACEI, blood pressure (tail cuff method) as well as PRA and urinary PGE2 excretion was determined. Renopapillary slices were obtained from some of the rats including controls and incubated to determine PGE2 synthesis. C or E administration resulted in a blood pressure decrease of 21 to 36 mm Hg with an increase in PRA. Urine volume and sodium excretion increased after daily treatment with C or E at 30 mg/kg. Urinary PGE2 excretion increased 1.4-fold in response to C, but not to E. Papillary PGE2 synthesis demonstrated a marked decrease 2 h after in vivo administration of either ACEI compared to controls. However, when C or enalaprilat was added in vitro to renal slices obtained from controls, only C at 10(-5) M showed a significant 2-fold increase in renal PGE2 synthesis. These results suggest that (1) renal PGE2 synthesis may be dependent on circulating angiotensin II. (2) C, but not enalaprilat, has a direct stimulatory effect on renal PGE2 synthesis and (3) renal PGE2 may not be involved very much in the hypotensive effect of ACEI.
由于血管紧张素转换酶抑制剂（ACEI）的降压机制之一被认为是通过肾脏激肽-前列腺素（PG）轴介导的，因此本研究旨在探讨卡托普利（C）或依那普利（E）对肾脏PGE2排泄或合成的影响。给体重200-250g的雄性Wistar大鼠口服30mg/kg/天的卡托普利或10或30mg/kg的依那普利，持续一周。在给予ACEI前后，测定血压（尾套法）以及肾素活性（PRA）和尿PGE2排泄量。从包括对照组在内的一些大鼠中获取肾乳头切片并进行孵育，以测定PGE2合成。给予C或E导致血压下降21至36mmHg，同时PRA升高。每日给予30mg/kg的C或E后，尿量和钠排泄增加。尿PGE2排泄量对C的反应增加了1.4倍，但对E无反应。与对照组相比，体内给予任一ACEI后2小时，乳头PGE2合成显著降低。然而，当在体外将C或依那普利拉添加到从对照组获得的肾切片中时，仅10^(-5)M的C显示肾PGE2合成显著增加2倍。这些结果表明：（1）肾脏PGE2合成可能依赖于循环中的血管紧张素II；（2）C而非依那普利拉对肾脏PGE2合成有直接刺激作用；（3）肾脏PGE2可能在很大程度上不参与ACEI的降压作用。
