Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine.
OBJECTIVE
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 ofvasoconstriction 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.
Azevedo
E R
ER
Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Schofield
A M
AM
Kelly
S
S
Parker
J D
JD
D000109:Acetylcholine; D000279:Administration, Cutaneous; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D005996:Nitroglycerin; D000109:Acetylcholine