The hypotensive action of captopril and enalapril is not prostacyclin dependent.
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.
Gerber
J G
JG
Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Franca
G
G
Byyny
R L
RL
LoVerde
M
M
Nies
A S
AS
D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004656:Enalapril / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
D004656:Enalapril; D002216:Captopril; D011464:Epoprostenol; D007213:Indomethacin