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Am J Physiol Heart Circ Physiol 285: H1428-H1434, 2003. First published May 29, 2003; doi:10.1152/ajpheart.00731.2002
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Endothelin receptor blockade has an oxygen-saving effect in Dahl salt-sensitive rats with heart failure

Teruo Noguchi, Zengyi Chen, Stephen P. Bell, Lori Nyland, and Martin M. LeWinter

Cardiology Unit, University of Vermont, Burlington, Vermont 05401

Submitted 23 August 2002 ; accepted in final form 23 May 2003

The effects of endothelin (ET) receptor blockade on energy utilization in heart failure (HF) are unknown. We administered ET type A (ETA), ET type B (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 O consumption (O2)-pressure-volume area relation. In HF, ETA and ETA/ETB but not ETB blockade decreased the contractility index (Emax)(–15 ± 3% and –17 ± 2%, P < 0.05), excitation-contraction (E-C) coupling O2 (–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 O2 (–24 ± 3% and –22 ± 2%, P < 0.05). Na+/H+ exchanger inhibition decreased Emax and E-C coupling O2 similar to ETA and ETA/ETB blockade, but did not alter efficiency. In HF, endogenous ET-1 maintains contractility at expense of increased O2 through ETA receptor activation, likely mediated by Na+/H+ exchange.

oxygen consumption


Address for reprint requests and other correspondence: M. M. LeWinter, Fletcher Allen Health Care, 111 Colchester Ave., Burlington, VT 05401 (E-mail: martin.lewinter{at}vtmednet.org).






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