Paradoxical vasoconstriction as result of acetylcholine and serotonin in diseased human coronary arteries.
In experimental atherosclerosis, impairment of endothelium-dependent vasodilation results in an unmasking of potent vasoconstrictor responses to serotonin, a substance released by aggregating platelets. To determine whether similar changes occur in diseased human coronary arteries, the responses to selective intracoronary infusions of acetylcholine and serotonin (both endothelium-dependent vasodilators) and to isosorbide dinitrate (a dilator directly acting on the smooth muscle) were assessed by quantitative coronary arteriography in 16 patients with angiographically normal coronary arteries, in 10 patients with minimal (less than 30% narrowing) and in five patients with more advanced (greater than 50% narrowing) coronary atherosclerosis. Acetylcholine induced constriction in diseased coronary arteries, but in patients with normal coronary arteriograms, it caused dilatation in seven patients (smooth dilators) and constriction in nine patients (smooth constrictors). In the smooth dilators, however, serotonin evoked no significant changes (+1.4 +/- 4.1%), whereas in the smooth constrictors and in patients with diseased coronary arteries, serotonin caused dose-dependent constriction. The vasoconstrictor responses to serotonin were similar in patients with minimal (-26.5 +/- 4.7%) and more advanced atherosclerosis (-30.9 +/- 5.3%). In one patient with coronary artery disease, serotonin caused a temporary coronary occlusion. All other patients dilated in response to isosorbide dinitrate. The vasomotor responses to acetylcholine and to serotonin were thus shown to be completely in parallel.


CONCLUSIONS
impairment of endothelium-dependent vasodilation unmasks potent vasoconstrictor responses to serotonin both in early and advanced coronary atherosclerosis. These changes may play an important role in the pathogenesis of a dynamic coronary artery stenosis.
Vrints
C J
CJ
Department of Cardiology, University Hospital of Antwerp, Belgium.
Bult
H
H
Bosmans
J
J
Herman
A G
AG
Snoeck
J P
JP
D000109:Acetylcholine / Q000494:pharmacology*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D012701:Serotonin; D007548:Isosorbide Dinitrate; D000109:Acetylcholine