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Cardiovascular Research 1998 39(3):617-624; doi:10.1016/S0008-6363(98)00205-3
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Comparison of the acute effects of a selective endothelin ETA and a mixed ETA/ETB receptor antagonist in heart failure

Masato Ohnishi, Atsuyuki Wada*, Takayoshi Tsutamoto, Daisuke Fukai and Masahiko Kinoshita

First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192, Japan

* Corresponding author. Tel.: +81-77-548-2213; Fax: +81-77-543-5839; E-mail: wada@belle.shiga-med.ac.jp

Objective: Both the selective endothelin (ET) ETA receptor and mixed ETA/ETB receptor antagonists improve haemodynamics in patients and experimental models with congestive heart failure (CHF) and reduce the mortality in CHF rats. However, it remains unclear which of these antagonists is superior in the treatment of CHF. In addition, there is little information as to whether these ET receptor antagonists contribute to the neuroendocrine regulation and body fluid balance. We therefore investigated the cardiorenal and neurohumoral benefits of selective ETA receptor and mixed ETA/ETB receptor antagonists in CHF. Methods: We administered acutely either the selective ETA receptor antagonist FR139317 (FR, n=6, 1 and 10 mg/kg) or the mixed ETA/ETB receptor antagonist TAK-044 (TAK, n=6, 1 and 3 mg/kg) to conscious dogs with CHF induced by rapid right ventricular pacing for ten days. Results: Both FR and TAK decreased the cardiac pressures and the plasma atrial natriuretic peptide level and increased the cardiac output and urinary sodium excretion. FR increased the urine flow rate in association with an increased glomerular filtration rate and renal plasma flow, while TAK reduced the plasma aldosterone level. Neither antagonist increased the plasma renin activity or norepinephrine levels. Conclusions: These findings suggest that a selective ETA receptor antagonist has more beneficial acute effects on renal functions in CHF than a mixed ETA/ETB antagonist. However, the long-term administration of a mixed ETA/ETB receptor antagonist would improve not only the haemodynamics but also prevent fluid retention by suppressing secretion of aldosterone during the treatment of chronic CHF.

KEYWORDS Heart failure; Endothelin; Antagonists; Neurohumoral factors; Dog


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