NITRATE TOLERANCE - INFLUENCE OF ISOSORBIDE DINITRATE ON THE HEMODYNAMIC AND ANTI-ANGINAL EFFECTS OF NITROGLYCERIN

[摘要] In a randomized, double blind, crossover study, 10 patients with stable exercise-induced angina pectoris were studied during acute and sustained therapy with oral isosorbide dinitrate. Circulatory changes and exercise performance were evaluated before, and 2 and 6 h after medication. Sublingual nitroglycerin was administered 30 min after the 2 and 6 h exercise tests, and the exercise test was repeated after another 5 min. Systolic blood pressure at rest 2 h after isosorbide dinitrate decreased by 25% during the acute phase, but by only 11% during the sustained phase (probability P < 0.05). Systolic blood pressure was not decreased further by nitroglycerin during acute therapy, but was decreased during sustained therapy (P < 0.05). Six hours after isosorbide dinitrate administration, systolic blood pressure remained significantly below the control value during sustained therapy. Treadmill walking time to moderate angina was significantly prolonged 2 h after isosorbide dinitrate administration during both the acute and sustained phases. During the sustained phase, there was no difference from control values after 6 h. Nitroglycerin did not increase walking time 2.5 h after isosorbide dinitrate during either acute (567 .+-. 122 vs. 560 .+-. 119 s) or sustained (582 .+-. 115 vs. 567 .+-. 129 s) therapy, but at 6.5 h, nitroglycerin increased walking time from 473 .+-. 125 to 547 .+-. 107 s (P < 0.05) during sustained therapy. Evidently, tolerance to the hemodynamic and antianginal effects of isosorbide dinitrate develops rapidly, nitroglycerin does not further prolong exercise duration 2.5 h after isosorbide dinitrate administration, nitroglycerin prolongs exercise duration when isosorbide dinitrate is no longer exerting a beneficial effect, and there is possible cross-tolerance between isosorbide dinitrate and nitroglycerin.