Antihypertensive effect of enalapril in essential hypertension: role of prostacyclin.
The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)
Oparil
S
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Department of Medicine, University of Alabama at Birmingham 35294.
Horton
R
R
Wilkins
L H
LH
Irvin
J
J
Hammett
D K
DK
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D004656:Enalapril / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D012083:Renin / Q000097:blood; D013467:Sulindac / Q000494:pharmacology
D013467:Sulindac; D000450:Aldosterone; D015121:6-Ketoprostaglandin F1 alpha; D004656:Enalapril; D011464:Epoprostenol; D012083:Renin; D007213:Indomethacin