Submitted on August 23, 2002
Accepted on May 23, 2003
Endothelin Receptor Blockade has an Oxygen-saving Effect in Dahl Salt Sensitive Rats with Heart Failure
Teruo Noguchi1, Zengyi Chen1, Stephen P. Bell1, Lori Nyland1, and Martin M. LeWinter1*
1 Cardiology Unit, University of Vermont, Burlington, VT, USA
* To whom correspondence should be addressed. E-mail: martin.lewinter{at}vtmednet.org.
Effects of endothelin (ET) receptor blockade on energy utilization in heart failure (HF) are unknown. We administered ETA, ETB and ETA/ETB antagonists to isolated hearts from Dahl salt-sensitive (DS) rats with HF and controls. Contractile efficiency was assessed as slope-1 of myocardial oxygen consumption (VO2) -pressure-volume area (PVA) relation. In HF, ETA and ETA/ETB but not ETB blockade decreased Emax (-15±3% and -17±2%, p<0.05), excitation-contraction (E-C) coupling VO2 (-39±4% and -37±5%, p<0.01), and efficiency (-15±4% and -17±2%, p<0.05). Despite decreased efficiency, ETA and ETA/ETB blockade decreased total VO2 (-24±3% and -22±2%, p<0.05). Na+/H+ exchanger inhibition decreased Emax and E-C coupling VO2 similar to ETA and ETA/ETB blockade, but did not alter efficiency. In HF, endogenous ET-1 maintains contractility at expense of increased VO2 through ETA receptor activation, likely mediated by Na+/H+ exchange.
