EndothelinB receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction

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, nonselective ET and ETB agonist, with ET-3, selective ETB receptor agonist. BACKGROUND Knowledge of the functional importance of ETB receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ET and ETB 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 pulmonary thermodilution catheter and an arterial line. RESULTS Endothelin-1 infusion led to systemic vasoconstriction, with 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 fall in cardiac index (2.44 ± 0.21 to 2.22 ± 0.20 liters/min/m2, p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with 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 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 similar magnitude at the same molar concentration. This suggests that ETB receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD.