Does chronic nitrate therapy induce tolerance to short-acting ones?

The aim of this study was to ascertain whether long-term nitrate administration (therapy by 120 mg ISDN or 16 mg molsidomine) decreases the efficiency of administered short-acting nitrate by the mechanism of tolerance. Fourteen male patients (mean age 56 years) with stabilized angina (IIIrd degree) were included and stress test with standard workload of 75 W was performed at the beginning of the study after cessation of therapy. Subsequently, the test was repeated after administration of 2.5 mg ISDN (IsoMack spray). The period of time until maximal load increased more than twice (4.0 +/- 1.3 vs 9.1 +2- 3.3 min. mean +/- SD). Afterward, patients were treated by ISDN 120 mg (IsoMack 120) once a day or molsidomine 8 mg (Corvaton ret.) twice a day; both drugs were interchanged after the period of 6 weeks. Stress tests were repeated at the end of these therapy periods (before and after application of short-acting nitrate). During 120 mg ISDN therapy, the time until maximal load after the application of 2.5 mg ISDN increased analogously (6.2 +/- 1.8 vs 9.6 +/- 3.7 min) and similarly after molsidomin therapy (5.5 +/- 1.7 vs 10.0 +/- 4.1 min). These results indicate that stress tolerance increases after short-acting nitrate administration significantly also in patients treated by high doses of long-acting nitrates (ISDN or molsidomine). Inducing of tolerance to short-acting nitrates was not observed.