Differential Effects of Selective and Non-Selective Prostaglandin-Synthesis Inhibition on the Pharmacological Responses to Captopril in Patients with Essential Hypertension

1. 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 PGF_1α 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 PGF_1α (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 PGF_1α, 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.