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