Endothelin-1 has a unique oxygen-saving effect by increasing contractile efficiency in the isolated rat heart

The effect of endothelin (ET)-1 on cardiac energetics is not fully understood.

In isolated, coronary-perfused rat hearts, we measured left ventricular contractility index (E(max)), pressure-volume area (PVA), and myocardial oxygen consumption (MVO(2)) before and after administration of ET-1 (1x10(-)(9) mol/L). ET-1 increased E(max) by 48+/-16% (P<0.01) and the total MVO(2) by 24+/-11% (P<0.01). The MVO(2)-PVA relations were linear both before and after ET-1 (r>0.99). ET-1 shifted MVO(2)-PVA upward, increasing the MVO(2) intercept by 24+/-13%. At the same time, ET-1 decreased the slope (S), with 1/S (contractile efficiency) being 46+/-5% before and 56+/-5% after ET-1 (P<0.01). ET-1-induced increases in E(max) and in contractile efficiency were abolished by an ET(A) receptor blocker (S-0139) but not by an ET(B) blocker (BQ-788). Although high [Ca(2+)] perfusion increased E(max) and the intercept to the same extent as ET-1, it did not change S. N(G)-Nitro-L-arginine (an inhibitor of nitric oxide synthase) increased the coronary perfusion pressure as much as ET-1, but S again remained unchanged. Dimethylamyloride (Na(+)/H(+) exchanger inhibitor) partially blocked the positive inotropic effect of ET-1 but not the ET-1-induced increase in the contractile efficiency.

Agonistic effects of ET-1 on the ET(A) receptor economized the chemomechanical conversion efficiency of the left ventricular unit myocardium by a mechanism independent of the Na(+)/H(+) exchanger. This unique oxygen-saving effect of ET-1 may play an adaptive role in the failing myocardium, in which local accumulation of ET-1 is present.