Early activation of cardiac and renal endothelin systems in experimental heart failure.

Motte, Sophie;Van Beneden, Ronald;Mottet, José;Rondelet, Benoît;McEntee, Kathleen;et.al.
(2003) American journal of physiology. Heart and circulatory physiology — Vol. 285, n° 6, p. H2482-91 (2003)

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Abstract
We investigated the time course of the expression of cardiac and renal endothelin systems in tachycardia-induced heart failure in dogs. Eleven beagles underwent rapid pacing at a progressively increased rate over a period of 5 wk, with a weekly clinical examination, echocardiography, measurement of circulating and urinary endothelin-1 (ET-1), and myocardial and renal tissue biopsies. Real-time quantitative PCR was used for determinations of tissue prepro-ET-1 (ppET-1), ET-1-converting enzyme (ECE-1), and ETA and ETB receptor mRNA. Cardiac and renal tissue ET-1 contents were evaluated by immunostaining and measured by radioimmunoassay at autopsy. Rapid pacing caused a progressive increase in end-systolic and end-diastolic ventricular volumes (P < 0.05) from week 2 together with a decrease in ejection fraction and in mean velocity of circumferential shortening (P < 0.05) from week 1. These changes were tightly correlated to myocardial ppET-1 and renal ETA receptor mRNA and less so to myocardial ECE-1 mRNA, and they occurred before any increase in plasma and urinary ET-1 (P < 0.05 from week 4) and clinical signs of heart failure. Renal ppET-1 did not change. Both cardiac and renal ET-1 peptide contents were increased at autopsy. We conclude that tachycardia-induced heart failure in dogs is characterized by an early activation of the cardiac and renal tissue endothelin systems, which occurs before any changes in circulating and urinary ET-1 and is closely related to altered ventricular function.
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Motte, S., Van Beneden, R., Mottet, J., Rondelet, B., Mathieu, M., Havaux, X., Lause, P., Clercx, C., Ketelslegers, J.-M., Naeije, R., & McEntee, K. (2003). Early activation of cardiac and renal endothelin systems in experimental heart failure. American journal of physiology. Heart and circulatory physiology, 285(6), H2482-91. https://doi.org/10.1152/ajpheart.00419.2003 (Original work published 2003)