Galler M, Backenroth R, Folkert V W, Schlondorff D
J Pharmacol Exp Ther. 1982 Jan;220(1):23-8.
In addition to their effect on angiotensin and bradykinin metabolism, converting enzyme inhibitors (CEI) may also alter prostaglandin (PG) synthesis. We therefore examined two CEI, SQ 14,225 (captopril) and SQ 20,881, for their in vitro effect on PG synthesis by glomeruli and aortic strips from rats. Glomeruli incubated in test tubes produced predominantly PGE2 and PGF2 alpha. Both CEI selectively stimulated PGE2 synthesis with maximal effects at 25 microM. During superfusion of glomeruli with captopril (25 microM) synthesis of PGE2 increased 5- to 10-fold and that of 6-keto-PGF1 alpha doubled. No significant change in PGF2 alpha or thromboxane B2 occurred. This effect of CEI was independent of angiotensin or bradykinin. In contrast captopril had no effect on PG synthesis by aortic strips, which produced predominantly prostacyclin assayed as 6-keto-PGR1 alpha and little PGE2 and PGF2 alpha. These results demonstrate that CEI can directly stimulate PG synthesis in glomeruli. This additional mechanism of action of CEI may require reinterpretation of the role of angiotensin based on results obtained with CEI.
除了对血管紧张素和缓激肽代谢的影响外,转换酶抑制剂(CEI)还可能改变前列腺素(PG)的合成。因此,我们研究了两种CEI,即SQ 14,225(卡托普利)和SQ 20,881,观察它们对大鼠肾小球和主动脉条PG合成的体外作用。在试管中孵育的肾小球主要产生前列腺素E2(PGE2)和前列腺素F2α(PGF2α)。两种CEI均选择性地刺激PGE2的合成,在25微摩尔时达到最大效应。在用卡托普利(25微摩尔)对肾小球进行灌流期间,PGE2的合成增加了5至10倍,而6-酮-前列腺素F1α(6-keto-PGF1α)的合成增加了一倍。PGF2α或血栓素B2没有明显变化。CEI的这种作用与血管紧张素或缓激肽无关。相比之下,卡托普利对主动脉条的PG合成没有影响,主动脉条主要产生作为6-酮-前列腺素F1α测定的前列环素,而PGE2和PGF2α很少。这些结果表明,CEI可以直接刺激肾小球中的PG合成。基于使用CEI获得的结果,CEI的这种额外作用机制可能需要重新解释血管紧张素的作用。