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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)