Author + information
- Received February 14, 2000
- Revision received May 30, 2000
- Accepted July 14, 2000
- Published online December 1, 2000.
- ↵*Reprint requests and correspondence to: Dr. Jules Y. T. Lam, Montreal Heart Institute, 5000 Bélanger East, Montreal, Quebec, Canada. H1T 1C8
The purpose of this study was to determine whether acute withdrawal of nitroglycerin (NTG) during hemodynamic tolerance is associated with platelet hypersensitivity.
Nitroglycerin is an effective antianginal medication but its use is limited by the development of tolerance and rebound. We have previously demonstrated a sustained inhibition of platelet function during continued use of NTG, but whether cessation of NTG is associated with an increase in platelet function that may contribute to rebound is unknown.
Normal porcine aortic media were exposed to flowing arterial blood from pigs (n = 8) treated continuously with NTG patches (Nitrodur 0.8 mg/h) for 48 h. Platelet function, blood pressure and the responses to angiotensin II infusion were evaluated before, during and after NTG treatment.
Mean arterial pressure fell by 15% after 3 h of treatment compared with control, returned to baseline by 48 h and increased significantly 2 h after drug removal. Autologous 51Cr-labelled platelet deposition on the aortic media was reduced by 30% after 48 h of continuous NTG administration compared with baseline (p = 0.02) and remained decreased 2 h after cessation of NTG therapy. Platelet aggregation to thrombin decreased in parallel to the decrease in platelet deposition. Blood pressure increase after intravenous injection of 10 μg of angiotensin II was blunted during treatment with NTG but increased significantly 2 h after cessation of nitrate therapy when compared with baseline.
Supersensitivity of the vessel wall to vasoconstrictors such as angiotensin 11, but not platelet hyperactivity, may contribute to the rebound phenomenon after acute nitrate withdrawal.
☆ Dr. Hébert was supported by the Faculté des Etudes Supérieures of the University of Montreal during PhD training. Dr. Lam was supported by the Medical Research Council of Canada and the Fonds de la Recherche en Santé du Québec, Montréal, Québec, Canada.
- Received February 14, 2000.
- Revision received May 30, 2000.
- Accepted July 14, 2000.
- American College of Cardiology