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ET-A receptor activity restrains coronary blood flow in the failing heart

Mingxiao Hou1, YingJie Chen, Jay H Traverse

  • 1Department of Medicine, University of Minnesota Health Sciences Center, Minneapolis, USA.

Journal of Cardiovascular Pharmacology
|May 29, 2004
PubMed

Insights

Endothelin-1 (ET-1) increases in heart failure. Blocking ET-A receptors improved coronary blood flow in dogs with heart failure, but did not increase oxygen use, suggesting ET-A does not limit oxygen in failing hearts.

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology
  • Heart Failure Research

Background:

  • Elevated endothelin-1 (ET-1) levels are observed in congestive heart failure (CHF).
  • Reduced coronary blood flow and myocardial oxygen consumption (MVO2) are features of some CHF models.
  • The role of ET-1 in limiting oxygen availability in the failing heart requires elucidation.

Purpose of the Study:

  • To test if ET-1-induced coronary vasoconstriction limits oxygen supply in the failing heart.
  • To investigate the effects of selective ET-A and ET-B receptor blockade on coronary blood flow during rest and exercise in CHF.
  • To determine if ET-A blockade improves oxygen delivery without increasing myocardial oxygen demand.

Main Methods:

  • Congestive heart failure was induced in 8 dogs via rapid ventricular pacing over 3-4 weeks.
  • Selective ET-A receptor blockade (BQ610) and ET-B receptor blockade (BQ788) were administered intracoronary.
  • Coronary blood flow, left ventricular pressure, and myocardial oxygen consumption were measured at rest and during graded treadmill exercise.

Main Results:

  • ET-B receptor blockade had no significant effect on left ventricular pressure or coronary blood flow in CHF dogs.
  • ET-A receptor blockade with BQ610 significantly increased coronary blood flow at rest and during exercise.
  • The enhanced coronary flow from ET-A blockade did not lead to increased myocardial oxygen uptake or left ventricular dP/dt.

Conclusions:

  • Selective ET-A receptor blockade modestly increases coronary blood flow in a canine model of congestive heart failure.
  • Despite increased coronary flow, ET-A blockade did not augment myocardial oxygen consumption.
  • These findings suggest that ET-A-mediated coronary vasoconstriction is not a primary limitation of oxygen uptake in this model of heart failure.

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