Interaction of indomethacin and nitroglycerin on hemodynamics and exercise tolerance in patients with angina pectoris

The influence of indomethacin therapy on the circulatory and antianginal effects of nitroglycerin were studied in six patients with stable angina pectoris. Indomethacin 50 mg or identical placebo capsules were administered three times a day for 1 week each in a double-blind, random manner. Heart rate, blood pressure, and ST-segment depression were measured at rest and during exercise before and after the administration of 0.6 mg sublingual nitroglycerin during indomethacin and placebo therapy. Nitroglycerin lowered standing systolic blood pressure by 38 mm Hg during placebo therapy (p less than 0.001) and by 36 mm Hg during indomethacin therapy (p less than 0.001). This was accompanied by a reflex increase in heart rate (p less than 0.001) which was of similar magnitude during placebo and indomethacin therapy. The increase in exercise duration to the onset of angina post nitroglycerin was similar during placebo and indomethacin therapy (128 vs 84 s; NS). Similarly, the increase in the total duration of exercise post nitroglycerin was similar during placebo and indomethacin therapy. Reduction in ST-segment depression post nitroglycerin was more pronounced during placebo than indomethacin therapy, but did not achieve statistical significance. The results show that indomethacin did not modify the circulatory effects of nitroglycerin at rest or during exercise and did not attenuate the increase in exercise tolerance produced by sublingual nitroglycerin. Since indomethacin is a potent prostaglandin inhibitor, the findings indirectly suggest that the vasodepressor and antianginal effects of nitroglycerin are in all probability not mediated by prostaglandins.