Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: Interaction with low dose acetylsalicylic acid

Abstract

1Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases.

2We investigated the effects of captopril (2×25 mg day⁻¹), or ASA (1×100 mg day⁻¹), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A₂ (2,3-dinor-TXB₂) and prostacyclin (2,3-dinor-6-keto-PGF_1α), and PGE₂ were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3− and cyclic GMP as indicators.

3Urinary 2,3-dinor-6-keto-PGF_1α excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB₂ excretion was inhibited by >80% by ASA alone or in combination with captopril (each P<0.05), but was not affected by captopril alone. Urinary PGE₂ excretion was not significantly changed by either of the treatments. Urinary NO3− and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination.

4Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone.

5Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB₂ excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.

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