Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries.
BACKGROUND
Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries.


RESULTS
In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A) receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a >50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (P<0.01).


CONCLUSIONS
ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.
Kinlay
S
S
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. skinlay@rics.bwh.harvard.edu
Behrendt
D
D
Wainstein
M
M
Beltrame
J
J
Fang
J C
JC
Creager
M A
MA
Selwyn
A P
AP
Ganz
P
P
D003324:Coronary Artery Disease / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D005996:Nitroglycerin / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents; D005996:Nitroglycerin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)