N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing.
Nitrates are well established in the treatment of angina pectoris and the presence of sulfhydryl groups seems to be fundamental to nitrate-induced vasodilatation. The present study was performed to elucidate if large oral doses of N-acetylcysteine (NAC, 2,400 mg X 2), a donor of sulfhydryl groups, given together with a single oral dose of the long-acting nitrate, isosorbide-5-mononitrate (5-ISMN, 60 mg), would modify the nitrate effect evaluated by exercise testing before and after additional sublingual doses of nitroglycerin (NTG). Ten patients with angina pectoris and angiographically proven significant coronary artery disease were included. All patients received a baseline therapy with beta blockers. None of the patients had developed nitrate tolerance at inclusion. NAC/5-ISMN treatment significantly prolonged the total exercise time as compared with placebo/5-ISMN (7.7 +/- 2.1 min vs. 6.8 +/- 1.7 min, p less than 0.05). This increase was of such magnitude that no further effect was obtained after additional NTG doses. This study demonstrated that increased availability of sulfhydryl groups can increase the exercise capacity in angina pectoris patients treated with 5-ISMN without nitrate tolerance.
Svendsen
J H
JH
Department of Cardiology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Klarlund
K
K
Aldershvile
J
J
Waldorff
S
S
D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000286:Administration, Sublingual; D000328:Adult; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005080:Exercise Test; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011897:Random Allocation
D003692:Delayed-Action Preparations; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D000111:Acetylcysteine