Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine

OBJECTIVES We sought to determine whether nitroglycerin (NTG) withdrawal co ntributes to worsening of endothelial dysfunction and development of the re bound phenomenon during intermittent transdermal NTG therapy. BACKGROUND Intermittent transdermal NTG therapy is recommended to avoid the development of tolerance. However, this regimen may precipitate worsening angina in the NTG-free interval. METHODS Twenty patients were randomized to intermittent transdermal NTG (0. 6 mg/h; NTG group) or no treatment (control group) five days before angiogr aphy. The risk factors for endothelial dysfunction were similar in both gro ups. After diagnostic angiography, the patients underwent quantitative angi ography before and after intracoronary acetylcholine (ACh), 10(-4) mol/lite r. Immediately after the morning study, the patch was removed from the NTG group, and 3 h later, the ACh infusion was repeated in both groups. All pat ients had mild to moderate coronary artery disease (CAD). RESULTS The diameter of the left anterior descending coronary artery at bas eline was 2.0 +/- 0.1 mm in the control group and 2.6 +/- 0.1 mm in the NTG group (p < 0.05). Acetylcholine caused mild vasoconstriction in the contro l group in the morning and afternoon (2.7 +/- 5.3% and 2.4 +/- 3.9%, respec tively; p = NS). The NTG group demonstrated mild vasoconstriction to ACh in the morning (3.2 +/- 2.8%; p = NS vs. control group). After patch removal, there was a significant increase in the magnitude of vasoconstriction in t he NTG group (11.6 +/- 3.9%, p = 0.04 vs, morning constriction). CONCLUSIONS These results confirm that NTG withdrawal increases the coronar y vasomotor response to ACh in patients with mild CAD and suggests that the rebound phenomena may be secondary to the development of endothelial dysfu nction after discontinuation of NTG therapy. (C) 2001 by the American Colle ge of Cardiology.