The physiological role of endogenous endothelin in the regulation of human coronary vasomotor tone.
OBJECTIVE
The study was done to investigate the physiological role of endogenous endothelin-1 in the human coronary circulation by studying the effect of an intracoronary infusion of the specific endothelin receptor subtype A (ETA) receptor antagonist BQ123 on coronary vasomotor tone.


BACKGROUND
Endothelin-1 contributes to the maintenance of peripheral vascular tone in humans. However, its physiological role in the human coronary vasculature is unknown.


METHODS
We studied 12 patients (mean age 54.7 +/- 2.5 years, 3 men) undergoing cardiac catheterization for investigation of atypical chest pain, with angiographically normal coronary arteries. Coronary artery cross-sectional area was measured with digital quantitative coronary angiography, and coronary blood flow was assessed with an intracoronary Doppler flow wire. Flow-mediated (adenosine, 18 microg) and agonist-mediated (substance P, 20 pmol/min for 2 min) endothelial responses were measured prior to study. BQ123 (40 nmol/min for 15 min and monitored for a further 15 min) was infused into the left coronary artery.


RESULTS
The BQ123 caused significant dilation of the proximal (artery cross-sectional area: 8.08 +/- 0.9 to 8.88 +/- 0.9 mm2; p < 0.05), mid (5.32 +/- 0.8 to 6.49 +/- 0.8 mm2; p < 0.001) and distal study vessel (2.11 +/- 0.2 to 2.50 +/- 0.2 mm2; p < 0.05). There was an increase in coronary blood flow (26.8 +/- 2.8 to 32.8 +/- 3.4 ml/min; p < 0.001) but no change in systemic hemodynamics. Baseline flow- or substance P-induced epicardial vasodilation did not correlate with the degree of vasodilation induced by BQ123.


CONCLUSIONS
These data uncover a role of endogenous endothelin-1 in the maintenance of basal vasomotor tone in patients with angiographically normal coronary arteries.
MacCarthy
P A
PA
Department of Cardiology, University Hospital of Wales, Cardiff, United Kingdom.
Pegge
N C
NC
Prendergast
B D
BD
Shah
A M
AM
Groves
P H
PH
D001783:Blood Flow Velocity / Q000502:physiology; D006328:Cardiac Catheterization; D003326:Coronary Circulation / Q000502:physiology*; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014655:Vascular Resistance / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology*
D019332:Endothelin-1