Hemodynamic and humoral interactions between perindopril and indomethacin in essential hypertensive subjects.
To evaluate whether perindopril, a carboxyl-containing new angiotensin-converting enzyme (ACE) inhibitor, exerts its antihypertensive action through the stimulation of prostaglandin synthesis, 10 uncomplicated essential hypertensive patients randomly received indomethacin (50 mg b.i.d.) or the corresponding placebo for 1 week and the reverse treatment after 2 weeks. Perindopril alone tended to reduce serum and urinary thromboxane B2 (TxB2) and to raise urinary 6-ketoPGF1 alpha and PGE2 and inhibited serum ACE activity 24 h post dosing by about 85%. Indomethacin, which significantly inhibited serum TxB2 and urinary TxB2, 6-ketoPGF1 alpha, and PGE2 without interfering with the inhibitory effect of perindopril on ACE, significantly reduced the antihypertensive action of perindopril alone by about 30%, but decreased though not significantly that of perindopril plus placebo. Although the size of the study limits the interpretation, these findings suggest that the stimulation of prostaglandin synthesis plays only a minor role in the antihypertensive action of perindopril.
Abdel-Haq
B
B
Clinica Medica I, University of Pisa, Italy.
Magagna
A
A
Favilla
S
S
Salvetti
A
A
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D020913:Perindopril; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D011897:Random Allocation; D012083:Renin / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D011453:Prostaglandins; D000450:Aldosterone; D013929:Thromboxane B2; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D007213:Indomethacin; D020913:Perindopril