TY - JOUR
T1 - Endothelin in thoracic inferior vena caval constriction model of heart failure
AU - Underwood, R. D.
AU - Aarhus, L. L.
AU - Heublein, D. M.
AU - Burnett, J. C.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - Recent studies have found endothelin-1 (ET), a potent vasoconstrictor of endothelial cell origin, is increased in congestive heart failure (CHF) in plasma and correlates with increased atrial pressures. Additionally, it has been shown that, despite increased circulating ET concentrations in CHF, a decreased responsiveness to exogenous ET infusion exists in an experimental model of CHF induced by rapid pacing. The present study was designed to determine whether plasma ET would be increased in a model of low cardiac output congestive failure without elevated atrial pressures produced by thoracic inferior vena caval constriction (TIVCC). In addition, we sought to determine whether this model of low cardiac output would show a full vasoconstrictive response to exogenous ET infusion and whether atrial natriuretic factor (ANF) infused acutely to achieve pathophysiological concentrations would modulate the systemic and renal hemodynamic responses to exogenous ET. Dogs were studied in the anesthetized state at 8-9 days after the TIVCC or sham operation. Baseline ET levels were significantly increased in the TIVCC dogs (n = 14) compared with sham operated dogs (n = 6; 41.4 ± 7.1 vs. 17.9 ± 1.5 pg/ml, respectively; P < 0.05). With exogenous ET infusion (5 ng · kg-1 · min-1), an intact systemic and renal vasoconstrictor response in the TIVCC dogs was observed. ANF prevented the systemic vascular and arterial pressure responses to ET. However, the potent renal vasoconstricting action of ET was not prevented by ANF. These studies suggest that ET may play an important role in maintaining blood pressure in the setting of low cardiac output. Additionally, they suggest ANF has an important counterregulatory role in the control of systemic hemodynamics.
AB - Recent studies have found endothelin-1 (ET), a potent vasoconstrictor of endothelial cell origin, is increased in congestive heart failure (CHF) in plasma and correlates with increased atrial pressures. Additionally, it has been shown that, despite increased circulating ET concentrations in CHF, a decreased responsiveness to exogenous ET infusion exists in an experimental model of CHF induced by rapid pacing. The present study was designed to determine whether plasma ET would be increased in a model of low cardiac output congestive failure without elevated atrial pressures produced by thoracic inferior vena caval constriction (TIVCC). In addition, we sought to determine whether this model of low cardiac output would show a full vasoconstrictive response to exogenous ET infusion and whether atrial natriuretic factor (ANF) infused acutely to achieve pathophysiological concentrations would modulate the systemic and renal hemodynamic responses to exogenous ET. Dogs were studied in the anesthetized state at 8-9 days after the TIVCC or sham operation. Baseline ET levels were significantly increased in the TIVCC dogs (n = 14) compared with sham operated dogs (n = 6; 41.4 ± 7.1 vs. 17.9 ± 1.5 pg/ml, respectively; P < 0.05). With exogenous ET infusion (5 ng · kg-1 · min-1), an intact systemic and renal vasoconstrictor response in the TIVCC dogs was observed. ANF prevented the systemic vascular and arterial pressure responses to ET. However, the potent renal vasoconstricting action of ET was not prevented by ANF. These studies suggest that ET may play an important role in maintaining blood pressure in the setting of low cardiac output. Additionally, they suggest ANF has an important counterregulatory role in the control of systemic hemodynamics.
KW - atrial natriuretic factor infusion
KW - endothelin infusion
KW - endothelium
KW - renal vasoconstriction
KW - systemic vasoconstriction
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U2 - 10.1152/ajpheart.1992.263.3.h951
DO - 10.1152/ajpheart.1992.263.3.h951
M3 - Article
C2 - 1415622
AN - SCOPUS:0026722105
SN - 0002-9513
VL - 263
SP - H951-H955
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3 32-3
ER -