Endothelin (ET)-converting enzyme (ECE) is a rate-limiting step in ET-1 generation, and its expression and activity are increased significantly with the development of congestive heart failure (CHF). The selective enzymic inhibition of ET-1 formation thus seems to be a very important target in the prevention of CHF. We evaluated the chronic effects of a specific ECE inhibitor, FR901533 (0.3mg·kg-1·h-1, n = 5) on cardiac, hormonal, and body fluid balance in dogs with CHF induced by rapid right ventricular pacing (270beats/min, 22 days). Vehicle dogs were given placebo (n = 5). Despite no significant difference in blood pressure, FR901533 decreased pulmonary capillary wedge pressure and increased cardiac output compared with the vehicle. FR901533 prevented the reduction of urine flow rate and urinary sodium excretion in association with an increase in the glomerular filtration rate and renal plasma flow compared with the vehicle. FR901533 also suppressed significantly the elevation of plasma atrial natriuretic peptide and aldosterone levels which is an established prognostic factor in CHF. These results indicate that the role of ECE in CHF is important and that chronic ECE inhibition could possess therapeutic potential in the treatment of CHF not only on haemodynamics but also in the prevention of fluid retention.
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September 2002
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Conference Article|
September 01 2002
Chronic effects of an endothelin-converting enzyme inhibitor on cardiorenal and hormonal function in heart failure
Atsuyuki WADA;
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
Dr A. Wada (e-mail [email protected]).
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Masato OHNISHI;
Masato OHNISHI
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
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Takayoshi TSUTAMOTO;
Takayoshi TSUTAMOTO
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
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Masanori FUJII;
Masanori FUJII
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
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Takehiro MATSUMOTO;
Takehiro MATSUMOTO
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
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Takashi YAMAMOTO;
Takashi YAMAMOTO
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
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Xinwen WANG;
Xinwen WANG
†Department of Vascular Surgery, First Teaching Hospital, China Medical University, Shenyang, People's Republic of China
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Masahiko KINOSHITA
Masahiko KINOSHITA
*First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 254S–257S.
Citation
Atsuyuki WADA, Masato OHNISHI, Takayoshi TSUTAMOTO, Masanori FUJII, Takehiro MATSUMOTO, Takashi YAMAMOTO, Xinwen WANG, Masahiko KINOSHITA; Chronic effects of an endothelin-converting enzyme inhibitor on cardiorenal and hormonal function in heart failure. Clin Sci (Lond) 1 September 2002; 103 (s2002): 254S–257S. doi: https://doi.org/10.1042/CS103S254S
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