Differential effects of N-acetylcysteine on nitroglycerin- and nicorandil-induced vasodilation in human coronary circulation.
We investigated the role of the availability of sulfhydryl groups during vasodilation of the human coronary circulation induced by nitroglycerin and nicorandil. In patients with normal coronary arteries (n = 29) or with coronary artery disease (CAD; n = 26), coronary blood flow (CBF) and epicardial coronary artery diameter after intracoronary administration of 50 microg nitroglycerin or 0.5 mg nicorandil were measured, before and after the intravenous infusion of saline or 100 mg/kg of N-acetylcysteine (NAC). In normal subjects, saline infusion did not alter the nitroglycerin- and nicorandil-induced vasodilation in large epicardial coronary artery. In contrast, NAC potentiated both nitroglycerin- and nicorandil-induced vasodilation. In patients with CAD, nitroglycerin and nicorandil induced less dilation than in normal subjects. NAC augmented the nitroglycerin- and nicorandil-induced vasodilation in the small epicardial coronary artery, but not in the large epicardial segments. In both groups, NAC potentiated the increase in CBF in response to nitroglycerin. However, NAC had no effects on the CBF response to nicorandil. Sulfhydryl availability is at least one determinant of the in vivo responsiveness to nitroglycerin of conductance and resistance vessels in normal human coronary circulation. In patients with CAD, external augmentation of sulfhydryl availability did not affect the depressed response to nitroglycerin in the large epicardial coronary artery. Although nicorandil acts as an NO donor, similar to nitroglycerin, in dilating the epicardial coronary artery, other effects, such as the opening of K(ATP) channel, play a more important role in the nicorandil-induced vasodilation of resistance vessels.
Department of Medicine, Tokyo Dental College and Ichikawa General Hospital, Japan.
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Y
Nishikawa
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Kanki
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Ogawa
D000111:Acetylcysteine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D005996:Nitroglycerin; D000111:Acetylcysteine