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(Circulation. 1997;95:1752-1754.)
© 1997 American Heart Association, Inc.

Articles

Reversing Congestive Heart Failure With Endothelin Receptor Antagonists

Yoshio Yazaki, MD, PhD; Tsutomu Yamazaki, MD, PhD

the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo (Japan) (Y.Y.), and Health Service Center, University of Tokyo (T.Y.).

Correspondence to Yoshio Yazaki, MD, PhD, Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo,7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Key Words: Editorials • congestive heart failure • endothelin

	Introduction

 
Eight years have passed since endothelin-1 (ET-1) was isolated from the supernatant of cultured porcine endothelial cells.¹ In addition to exerting potent and prolonged vasoconstrictor effects on both venous and arterial smooth muscle cells, ET-1 has a diverse set of biological activities (such as positive inotropic² and chronotropic³ effects on cardiac myocytes, proliferative effects on various cells,⁴ and stimulation of hormone release and modulation of central nervous activities⁵ ). Moreover, it has recently been elucidated that the mice homozygous for ET-1 null mutation represent not only cardiovascular malformations but also morphological abnormalities of the pharyngeal arch–derived craniofacial tissues and organs,^{6 7} indicating that ET-1 is essential to normal embryonic development. To date, ET-1 is known to be the sole vasoactive peptide that is involved in normal morphogenesis. Furthermore, a recent in vitro study has confirmed the involvement of ET-1 as an autocrine factor in pressure overload–induced cardiac hypertrophy.⁸

Many studies have found that the ET-1 level is increased in the plasma of symptomatic congestive heart failure (CHF) patients,^{9 10 11 12 13 14} and the concentrations increase as the severity of CHF increases. Namely, the elevation of circulating ET-1 levels in CHF has been shown to be negatively correlated with left ventricular ejection fraction (LVEF) and cardiac index and positively correlated with New York Heart Association functional class, left ventricular (LV) end-diastolic volume index,¹⁵ left atrial pressure,¹⁶ and extent of pulmonary hypertension.¹⁰ Moreover, plasma ET-1 levels in the subacute phase after myocardial infarction provide prognostic information independent of clinical and biochemical variables including patient age, previous . . . [Full Text of this Article]

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