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Endothelin B receptors are functionally important in mediating vasoconstriction in the systemic circulation in
P J Cowburn1, J G Cleland, J D McArthur
1Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Department of Cardiology, Scotland, United Kingdom.
Insights
Endothelin receptor B (ETB) agonists, ET-1 and ET-3, caused similar systemic vasoconstriction in patients with left ventricular systolic dysfunction (LVSD). This indicates ETB receptors play a key role in vasoconstriction within the systemic circulation of LVSD patients.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Endocrinology
Background:
- Endothelin-1 (ET-1) is implicated in vasoconstriction in chronic heart failure.
- Understanding the role of endothelin B (ETB) receptors is crucial for developing effective heart failure treatments.
- Determining if ETB receptor antagonists are necessary alongside ET(A) antagonists to block ET-1's vasoconstrictive effects.
Purpose of the Study:
- To evaluate the functional significance of ETB receptors in patients with left ventricular systolic dysfunction (LVSD).
- To compare the hemodynamic responses to ET-1 (nonselective ET(A)/ETB agonist) and ET-3 (selective ETB agonist).
Main Methods:
- Two groups of eight LVSD patients received infusions of ET-1 or ET-3 at two concentrations (5 and 15 pmol/min).
- Hemodynamic parameters were monitored using pulmonary thermodilution catheter and arterial line.
- Baseline hemodynamic indices were similar between the two patient groups.
Main Results:
- Both ET-1 and ET-3 infusions induced systemic vasoconstriction, increasing mean arterial pressure and systemic vascular resistance.
- Cardiac index decreased significantly following infusions of both ET-1 and ET-3.
- Pulmonary hemodynamics remained largely unchanged in both infusion groups.
- The magnitude of hemodynamic changes was similar between ET-1 and ET-3 at equivalent molar concentrations.
Conclusions:
- ETB receptors are functionally significant in mediating systemic vasoconstriction in patients with LVSD.
- The similar vasoconstrictive effects of ET-1 and ET-3 suggest a substantial role for ETB receptor activation.
- These findings have implications for understanding endothelin's role in heart failure pathophysiology.
Objectives:
This study was designed to assess the functional importance of endothelin (ET)B receptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ET(A) and ET(B) agonist, with ET-3, a selective ET(B) receptor agonist.
Background:
Knowledge of the functional importance of ET(B) receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ET(A) and ET(B) receptors are required to fully prevent vasoconstriction to endogenously produced ET-1.
Methods:
We infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line.
Results:
Endothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean +/- SEM 100 +/- 3 to 105 +/- 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 +/- 142 to 2,055 +/- 164 dyn/s/cm(-5), p < 0.001) and a fall in cardiac index (2.44 +/- 0.21 to 2.22 +/- 0.20 liters/min/m , p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 +/- 6 to 105 +/- 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 +/- 210 to 1,918 +/- 245 dyn/s/cm(-5), p < 0.01) and a fall in cardiac index (2.66 +/- 0.28 to 2.42 +/- 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group.
Conclusions:
Both ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ET(B) receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD.