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(Circulation. 2001;103:1557.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Endothelin-1 Has a Unique Oxygen-Saving Effect by Increasing Contractile Efficiency in the Isolated Rat Heart

Yuzo Takeuchi, MD; Yasuki Kihara, MD, PhD; Koichi Inagaki, MD, PhD; Takeshi Yoneda, MD; Shigetake Sasayama, MD, PhD

From the Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Correspondence to Yasuki Kihara, MD, PhD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail kihara{at}kuhp.kyoto-u.ac.jp

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

Methods and Results—In isolated, coronary-perfused rat hearts, we measured left ventricular contractility index (E_max), pressure-volume area (PVA), and myocardial oxygen consumption (MO₂) 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 MO₂ by 24±11% (P<0.01). The MO₂-PVA relations were linear both before and after ET-1 (r>0.99). ET-1 shifted MO₂-PVA upward, increasing the MO₂ 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 [Ca²⁺] 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.

Conclusions—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.

Key Words: endothelin • oxygen • mechanics • contractility

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