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Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing
Z S Kyriakides1, D T Kremastinos, E Bofilis
12nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. zskyr@otenet.gr
Insights
Endogenously generated endothelin-1 (ET-1) stimulates endothelin type A (ET(A)) receptors, contributing to human coronary vascular tone. Blocking ET(A) receptors with BQ-123 increased coronary artery diameter and blood flow.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Endothelin Receptor Antagonism
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor peptide.
- The role of endothelin type A (ET(A)) receptors in maintaining human coronary vascular tone is not fully understood.
Purpose of the Study:
- To investigate the contribution of endothelin type A (ET(A)) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans.
Main Methods:
- A controlled clinical study involving 14 subjects (7 healthy, 7 with coronary artery disease).
- Infusion of BQ-123, a selective ET(A) receptor antagonist, into the left coronary artery.
- Measurement of coronary artery diameter and blood flow velocity using coronary arteriography and Doppler flow guidewire.
Main Results:
- BQ-123 infusion significantly increased proximal (6%) and distal (12%) left anterior descending coronary artery diameter.
- Coronary blood flow increased by 23% and coronary vascular resistance decreased by 28% post-BQ-123 infusion.
- Patients with and without coronary artery disease showed similar responses to BQ-123.
Conclusions:
- Endogenously produced ET-1, via ET(A) receptor stimulation, contributes to basal coronary artery tone in humans.
- The specific role of endothelin type B (ET(B)) receptors in this process requires further investigation.
Objective:
To examine the contribution of endothelin type A (ET(A)) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans.
Design:
Controlled clinical study.
Setting:
Tertiary cardiovascular referral centre.
Patients:
14 subjects were studied, seven with normal coronary arteries and seven with coronary artery disease, mean (SEM) age, 53 (2) years.
Interventions:
After diagnostic coronary arteriography, BQ-123 (a selective ET(A) receptor antagonist; 100 nmol/min) in 0.9% saline, was infused into the left coronary artery at a rate of 1 ml/min for 60 minutes. Eight control subjects received saline alone.
Main Outcome Measures:
Blood flow velocity in the left anterior descending coronary artery, measured using a Doppler flow guidewire; coronary arteriography performed at baseline and immediately at the end of the BQ-123 or saline infusion to measure the diameter of proximal and distal left anterior descending coronary artery segments.
Results:
The diameter of the proximal segment increased by 6 (2)%, while that of the distal segment increased by 12 (3)% after BQ-123 (both p < 0.05 v baseline). Coronary blood flow increased from 75 (10) to 92 (10) ml/min and coronary vascular resistance decreased from 1.99 (0.36) to 1.44 (0. 22) mm Hg/ml/min after BQ-123 (both p < 0.05 v baseline). The response to BQ-123 of patients with and without coronary artery disease was similar. There was no effect of saline in the controls.
Conclusions:
Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans by ET(A) receptor stimulation. The role of ET(B) receptors remains to be defined.