Circulation, Vol 87, 80-85, Copyright © 1993 by American Heart Association
P Collins, J Burman, HI Chung and K Fox
BACKGROUND. The endothelium can regulate vascular tone by releasing both
endothelium-derived relaxing factor (EDRF or nitric oxide) and contracting
factors. To date, there has only been circumstantial evidence to indicate
EDRF activity in vivo in human coronary arteries. Using human hemoglobin as
a specific inhibitor, the hypothesis that acetylcholine-induced coronary
vasodilation is due to EDRF release was tested. METHODS AND RESULTS. We
studied the response of normal coronary arteries to acetylcholine (an
endothelium-dependent vasodilator) and isosorbide dinitrate (an
endothelium-independent vasodilator) in seven patients. The specificity of
any vasodilator response was assessed by the infusion of reduced free human
hemoglobin. Hemoglobin 10(-5) M infusion alone had no effect on coronary
artery diameter. Drugs were infused into the coronary artery, and the
diameter changes were assessed by quantitative angiography. Acetylcholine
10(-7) M increased left anterior descending coronary artery diameter from
control: 2.30 +/- 0.12 mm to 2.79 +/- 0.20 mm (mean +/- SEM, n = 7, p <
0.01). Hemoglobin both in a concentration of 10(-6) M and 10(-5) M reversed
this vasodilator effect, causing constriction to 2.11 +/- 0.18 mm (p <
0.001 compared with acetylcholine 10(-7) M) and 2.29 +/- 0.14 mm (p <
0.05 compared with acetylcholine 10(-7) M). Isosorbide dinitrate in the
presence of hemoglobin caused dilatation of the coronary artery in all
cases to 3.04 +/- 0.24 mm (p < 0.001 compared with acetylcholine 10(-7)
M and hemoglobin 10(-6) M). CONCLUSIONS. Using a specific inhibitor of
nitric oxide, reduced free hemoglobin, we have demonstrated that basal EDRF
release does not appear to play an important role in the maintenance of
human epicardial coronary artery diameter in vivo but is responsible for
the acetylcholine-induced dilatation.
ARTICLES
Hemoglobin inhibits endothelium-dependent relaxation to acetylcholine in human coronary arteries in vivo
Department of Cardiac Medicine, National Heart and Lung Institute, London, UK.
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