Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure

OBJECTIVES: This study was done to determine the spillover and extraction of endothelin-1 (ET-1) in the peripheral circulation, and to evaluate the factors that regulate local ET-1 extraction in the peripheral circulation in patients with congestive heart failure (CHF). BACKGROUND: The relationship between the spillover and extraction of the ET-1 in the peripheral circulation and systemic vascular resistance (SVR) has not been fully clarified. METHODS: We measured plasma levels of ET-1 both in femoral artery (FA) and femoral vein (FV) in 93 patients with CHF. RESULTS: Plasma ET-1 was significantly higher in FV than in FA in New York Heart Association (NYHA) functional class II patients, but there was no difference of ET-1 between FA and FV in functional class III patients. In patients with functional class IV, plasma ET-1 was significantly lower in FV than in FA, and SVR was significantly higher than in patients with NYHA class II or class III. Moreover, a significant positive correlation existed between plasma ET-1 extraction across the lower leg and SVR in these patients. Among the various neurohumoral factors and hemodynamics, plasma levels of ET-1, angiotensin II in the FA showed an independent and significant relationship with the plasma arteriovenous difference of ET-1 in the lower limb. CONCLUSIONS: Circulating ET-1 is extracted in peripheral circulation in patients with severe CHF, suggesting the possibility of upregulation of ET receptors of vascular beds in the lower limb in these patients. The peripheral extraction of ET-1 correlates with SVR in severe CHF patients and is mainly regulated by the local ET-1 and renin angiotensin systems.