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Increased endothelin in experimental heart failure
K B Margulies1, F L Hildebrand, A Lerman
1Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minn. 55905.
Insights
Circulating endothelin levels are significantly elevated in experimental congestive heart failure (CHF). Elevated endothelin is a sensitive indicator of CHF and may play a role in its pathophysiology.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
Background:
- Endothelin is a potent vasoconstrictor peptide found in normal plasma.
- The role of endothelin in pathophysiological states is not well understood.
Purpose of the Study:
- To investigate if circulating endothelin concentrations increase in experimental congestive heart failure (CHF).
- To test the hypothesis that endothelin contributes to CHF pathophysiology.
Main Methods:
- Induction of CHF in dogs via rapid ventricular pacing.
- Measurement of plasma endothelin levels in dogs with CHF and control dogs.
- Correlation analysis between endothelin levels and hemodynamic parameters (right atrial pressure, pulmonary capillary wedge pressure).
Main Results:
- Plasma endothelin levels were significantly higher in dogs with CHF compared to controls (20.4 +/- 1.4 vs. 9.7 +/- 0.9 pg/ml, p < 0.0001).
- Plasma endothelin > 14.0 pg/ml was a sensitive and specific indicator of significant CHF.
- Endothelin levels correlated independently with right atrial pressure and pulmonary capillary wedge pressure in CHF dogs.
Conclusions:
- Circulating endothelin is elevated in experimental congestive heart failure.
- Increased endothelin may contribute to the pathophysiology of CHF.
- Endothelin warrants further investigation as a therapeutic target in heart failure.
Abstract:
Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced.