Gerber J G, Franca G, Byyny R L, LoVerde M, Nies A S
Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Clin Pharmacol Ther. 1993 Nov;54(5):523-32. doi: 10.1038/clpt.1993.184.
Angiotensin converting enzyme inhibitors have been proposed to have a prostaglandin-dependent component to their hypotensive action. The aim of this study was to assess whether the structurally dissimilar angiotensin converting enzyme inhibitors captopril and enalapril stimulate the synthesis of prostacyclin, whether their hypotensive action is blunted by indomethacin, and whether these biochemical or physiologic parameters differ for the two drugs, in white subjects with essential hypertension. Twelve patients were enrolled and 11 finished the study. The study consisted of a double blind, randomized, double-crossover design. All patients received either placebo or 50 mg indomethacin twice a day for 3 weeks; after 1 week of placebo or indomethacin either 50 mg captopril or 10 mg enalapril twice a day was added and continued for 2 weeks. Each patient received every possible combination. Neither captopril nor enalapril stimulated prostacyclin production as determined by measurement of the urinary excretion rate of its main enzymatic metabolite, 2,3-dinor-6-keto-prostaglandin-F1 alpha. Although indomethacin reduced the urinary excretion of the enzymatic metabolite of prostacyclin by more than 50%, it did not influence the hypotensive effect of captopril or enalapril. We conclude that neither captopril nor enalapril have a significant prostacyclin-dependent component to their hypotensive action.
血管紧张素转换酶抑制剂被认为其降压作用有一个依赖前列腺素的成分。本研究的目的是评估结构不同的血管紧张素转换酶抑制剂卡托普利和依那普利是否刺激前列环素的合成，它们的降压作用是否被吲哚美辛减弱，以及在原发性高血压白人受试者中这两种药物的这些生化或生理参数是否不同。12名患者入组，11名完成研究。该研究采用双盲、随机、双交叉设计。所有患者接受安慰剂或吲哚美辛50毫克每日两次，共3周；在接受安慰剂或吲哚美辛1周后，加用卡托普利50毫克或依那普利10毫克每日两次，并持续2周。每位患者接受了所有可能的组合。通过测量其主要酶代谢产物2,3-二去甲-6-酮-前列腺素-F1α的尿排泄率确定，卡托普利和依那普利均未刺激前列环素的产生。虽然吲哚美辛使前列环素的酶代谢产物的尿排泄减少超过50%，但它并未影响卡托普利或依那普利的降压作用。我们得出结论，卡托普利和依那普利的降压作用均没有显著的依赖前列环素的成分。
