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Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine.

Abstract：

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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Caramori PR,Adelman AG,Azevedo ER,Newton GE,Parker AB,Parker JD

doi

10.1016/s0735-1097(98)00456-2

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

1969-74

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(98)00456-2

journal_volume

pub_type

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Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine.