CHRONIC ADMINISTRATION OF N-ACETYLCYSTEINE FAILS TO PREVENT NITRATE TOLERANCE IN PATIENTS WITH STABLE ANGINA-PECTORIS

1. Reduced availability of sulphydryl groups in vascular smooth muscle cells may contribute to the development of tolerance to the action of the organic nitrovasodilators. 2. Eight patients with stable angina were treated with 10 mg of transdermal glyceryl trinitrate per 24 h, together with 400 mg N‐acetylcysteine, a sulphydryl group donor, or matching placebo three times daily in a double‐blind randomised crossover manner for two periods of 4 days with intervening washout period of 3 days off these drugs. Other therapy remained unaltered during the study. 3. Blood pressure, heart rate and symptom‐limited treadmill walking time were measured in the pre‐treatment control state and 4 h after starting treatment on day 1 and day 4 of each glyceryl trinitrate treatment period. 4. The changes seen on day 1 were attenuated by day 4 to an equal extent in N‐acetylcysteine and placebo treatment periods. 5. These results suggest that chronic oral administration of N‐acetylcysteine fails to prevent the development of tolerance to the anti‐anginal or haemodynamic effects of glyceryl trinitrate. 1990 The British Pharmacological Society