Key result
Indomethacin increases BP and lowers urinary 6-keto PGF1α versus sulindac in patients taking captopril.
Why the study?
Does indomethacin compared to sulindac differentially affect the pharmacological and blood pressure responses to captopril in patients with essential hypertension?
RCT (n=5)
cross-over
Does indomethacin compared to sulindac differentially affect the pharmacological and blood pressure responses to captopril in patients with essential hypertension?
p-value: p=<0.02
Non-selective prostaglandin inhibition with indomethacin blunts the antihypertensive effect of captopril more than selective inhibition with sulindac, highlighting the role of renal prostaglandins in ACE inhibitor efficacy.
Indomethacin attenuates captopril's antihypertensive effect; confirms renal prostaglandins mediate ACE inhibitor efficacy.
The finding that sulindac, in contrast to indomethacin, does not inhibit renal prostaglandins synthesis in humans, prompted us to study the role that systemic and/or renal prostaglandins can play in the pharmacological responses to captopril. According to a randomized cross-over design, we compared the short-term (1 week) effect of indomethacin (50 mg twice daily) and of sulindac (200 mg twice daily) on blood pressure, plasma renin activity (PRA), angiotensin converting enzyme (ACE), serum thromboxane (TX) B2 and urinary 6-keto PGF1α of five essential hypertensive patients on chronic treatment with captopril (100-200 mg twice daily). 2. Indomethacin significantly increased systolic (P < 0.02) and diastolic (P < 0.02) blood pressure, decreased PRA (P < 0.05), serum TXB2 (P < 0.001) and urinary 6-keto PGF1α (P < 0.001) and did not change ACE. 3. Sulindac reduced PRA (P < 0.02) and serum TXB2 (P < 0.001) to the same extent as indomethacin, but it did not change ACE and urinary 6-keto PGF1α, and caused only a small and significant increment of blood pressure. 4. These preliminary findings confirm that sulindac selectivity inhibits prostaglandins synthesis and seem to indicate that renal PGI2 can play a role in the antihypertensive action of captopril.
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Salvetti et al. (1982) conducted an RCT in essential hypertension (n=5). Indomethacin and Sulindac vs. Cross-over comparison was evaluated on blood pressure, plasma renin activity, angiotensin converting enzyme, serum thromboxane B2 and urinary 6-keto PGF1α (p=<0.02). Indomethacin significantly increased blood pressure (P<0.02) and decreased urinary 6-keto PGF1α (P<0.001) in patients on captopril, whereas sulindac did not change urinary 6-keto PGF1α.
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