Hemoglobin inhibits endothelium-dependent relaxation to acetylcholine in human coronary arteries in vivo.
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.


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.
Collins
P
P
Department of Cardiac Medicine, National Heart and Lung Institute, London, UK.
Burman
J
J
Chung
H I
HI
Fox
K
K
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000328:Adult; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D006454:Hemoglobins; D011189:Potassium Chloride; D000109:Acetylcholine