title: Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: interaction with low dose acetylsalicylic acid.
abstract: 1. Angiotensin 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. 2. We investigated the effects of captopril (2 x 25 mg day-1), or ASA (1 x 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-PGF1 alpha), 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. 3. Urinary 2,3-dinor-6-keto-PGF1 alpha 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. 4. Blood 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. 5. Captopril 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.
authors.affiliation: Institute of Clinical Pharmacology, Medical School, Hannover, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Böger
authors.forename: S M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: P
authors.initials: P
authors.lastname: Kramme
authors.forename: D
authors.initials: D
authors.lastname: Tsikas
authors.forename: F M
authors.initials: FM
authors.lastname: Gutzki
authors.forename: J C
authors.initials: JC
authors.lastname: Frölich
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D011464:Epoprostenol / Q000096:biosynthesis* / Q000652:urine; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000652:urine; D011863:Radioimmunoassay; D013268:Stimulation, Chemical
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D007457:Iodine Radioisotopes; D009569:Nitric Oxide; D002216:Captopril; D011464:Epoprostenol; D001241:Aspirin