Effect of atenolol and celiprolol on acetylcholine-induced coronary vasomotion in coronary artery disease.
Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3x10(-7), 2.0x10(-6), and 6.3x10(-6) M) was given before and after double-blind celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3x12 patients. Vasomotion was investigated by quantitative coronary angiography in proximal and distal segments of epicardial coronary arteries, and by the determination of the coronary resistance index based on Doppler-flow measurements. The investigated drugs had no direct affect on the diameter of the epicardial coronary arteries. However, celiprolol, in contrast to atenolol, significantly reduced systemic vascular resistance (change after atenolol: from 1,855+/-308 to 2,161+/-550 dyne s cm(-5); celiprolol: 1,691+/-435 to 1,411+/-343 dyne s cm(-5); and placebo: 1,722+/-215 to 1,710+/-213 dyne s cm(-5), p<0.001) and the coronary resistance index (change after atenolol: 2.52+/-3.58 to 2.86+/-4.24; celiprolol: 2.70+/-1.55 to 2.49+/-2.26; and placebo: 1.97+/-1.35 to 1.92+/-1.25, p<0.01). Celiprolol, atenolol, and placebo did not have different effects on acetylcholine-induced coronary vasomotion of epicardial conductance vessels (diminution of proximal lumen diameter before/after atenolol: 0.42+/-0.39/0.44+/-0.39 mm; celiprolol: 0.32+/-0.26/0.30+/-0.24 mm; and placebo: 0.36+/-0.29/0.43+/-0.40 mm) and of coronary resistance vessels (reduction of coronary resistance index before/after atenolol: 1.95 +/-4.74/ 1.92+/-3.74; celiprolol: 0.98+/-0.73/1.41+/-1.50; and placebo: 1.16+/-1.29/1.16+/-1.04). In contrast to atenolol, celiprolol possesses vasodilative properties in systemic and coronary resistance vessels. There was no direct effect on the diameter of conductance vessels. Acetylcholine-induced coronary vasomotion both in conductance and resistance vessels was not influenced by the beta blockers that were studied. This suggests that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide related vasomotion.
Burger
W
W
Department of Interventional Cardiology, St Georg Hospital, Leipzig, Germany.
Hampel
C
C
Kaltenbach
M
M
Hartmann
A
A
Herrmann
M
M
Hoffmann
J A
JA
Klepzig
H
H
D000109:Acetylcholine / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology*; D017272:Celiprolol / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D014665:Vasodilator Agents; D001262:Atenolol; D017272:Celiprolol; D000109:Acetylcholine