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CLINICAL STUDIES

Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine

^a Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
^* SOCAR Cardiac Research, Toronto, Ontario, Canada

Manuscript received April 10, 1998; revised manuscript received July 8, 1998, accepted August 6, 1998.

Address for correspondence: Dr. John D. Parker, Mount Sinai Hospital, 600 University Avenue, Suite 1609, Toronto, Ontario, Canada
jdp{at}inforamp.net

Objectives. The purpose of this study was to investigate whether therapy with nitroglycerin (GTN) would lead to abnormal coronary artery responses to the endothelium-dependent vasodilator acetylcholine.

Background. Nitroglycerin therapy is associated with specific biochemical changes in the vasculature that may lead to increased vascular sensitivity to vasoconstrictors.

Methods. Patients were randomized to continuous transdermal GTN, 0.6 mg/h (n = 8), or no therapy (n = 7), for 5 days prior to a diagnostic catheterization. Patients had similar risk factors for endothelial dysfunction. Quantitative angiography was performed in the morning to measure the mean luminal diameter of the left anterior descending coronary artery (LAD) in response to intracoronary acetylcholine (peak concentration, 10^–4 mol/liter). The transdermal preparation was removed from the GTN group, and 3 h later experimental procedures were repeated.

Results. In the morning, the GTN group experienced greater coronary constriction in response to acetylcholine infusion than those not receiving GTN (–19.6 ± 4.2 vs. –3.8 ± 3.0%; p = 0.01). Three hours later, the GTN group continued to display greater constriction to acetylcholine (–24.1 ± 5.9%) as compared to the non-GTN group (–1.8 ± 4.8%). When the morning and afternoon responses to acetylcholine were compared, the increase in coronary constriction in the GTN group was greater than the change observed in the non-GTN group (p < 0.05).

Conclusions. This study demonstrates that therapy with GTN causes abnormal coronary vasomotor responses to the endothelium-dependent vasodilator acetylcholine, changes that were persistent for up to 3 hours after GTN discontinuation. This nitrate-associated vasomotor dysfunction has implications with respect to the development of nitrate tolerance and the potential for adverse events during nitrate withdrawal.

Abbreviations and Acronyms   GTN = nitroglycerin   LAD = left anterior descending coronary artery

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