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CLINICAL STUDY: ENDOTHELIAL FUNCTION

Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine

^a Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

Manuscript received April 14, 2000; revised manuscript received September 11, 2000, accepted October 16, 2000.

Reprint requests and correspondence: Dr. John D. Parker, Mount Sinai Hospital, 600 University Avenue, Suite 1609, Toronto, Ontario M5G-1X5
jdp{at}inforamp.net

OBJECTIVES

We sought to determine whether nitroglycerin (NTG) withdrawal contributes to worsening of endothelial dysfunction and development of the rebound 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 angiography. The risk factors for endothelial dysfunction were similar in both groups. After diagnostic angiography, the patients underwent quantitative angiography before and after intracoronary acetylcholine (ACh), 10^–4 mol/liter. 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 patients had mild to moderate coronary artery disease (CAD).

RESULTS

The diameter of the left anterior descending coronary artery at baseline 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 control group in the morning and afternoon (2.7 ± 5.3% and 2.4 ± 3.9%, respectively; 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 the NTG group (11.6 ± 3.9%, p = 0.04 vs. morning constriction).

CONCLUSIONS

These results confirm that NTG withdrawal increases the coronary vasomotor response to ACh in patients with mild CAD and suggests that the rebound phenomena may be secondary to the development of endothelial dysfunction after discontinuation of NTG therapy.

Abbreviations and Acronyms   ACh = acetylcholine   CAD = coronary artery disease   Cx = circumflex coronary artery   D5W = 5% dextrose in water   LAD = left anterior descending coronary artery   LMCA = left main coronary artery   NTG = nitroglycerin

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