CLINICAL STUDY: CORONARY PHYSIOLOGY
The physiological role of endogenous endothelin in the regulation of human coronary vasomotor tone
Philip A. MacCarthy, BSc, PhD, MRCP*,
Nicholas C. Pegge, MA, MBBS, MRCP*,
Bernard D. Prendergast, MD, BMedSci, MRCP*,
Ajay M. Shah, MD, FRCP, FESC and
Peter H. Groves, MBBS, MD, FRCP*
* Department of Cardiology, University Hospital of Wales, Heath Park, Cardiff, United Kingdom
GKT School of Medicine, King’s College London, Bessemer Road, London, United Kingdom
Manuscript received February 2, 2000;
revised manuscript received June 12, 2000,
accepted September 7, 2000.
Reprint requests and correspondence: Dr. Peter H. Groves, Consultant Cardiologist, Department of Cardiology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW, United Kingdom
OBJECTIVES
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 µg) 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.
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Abbreviations and Acronyms
| | APV | = average peak (Doppler) velocity | | Cx | = circumflex coronary artery | | ET | = endothelin | | ETA/ETB | = endothelin receptor subtype A/B | | GTN | = glyceryl trinitrate | | LAD | = left anterior descending coronary artery | | NO | = nitric oxide |
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