Early activation of cardiac and renal endothelin systems in experimental heart failure.
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.
Motte
Sophie
S
Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Brussels B-1070, Belgium.
van Beneden
Ronald
R
Mottet
José
J
Rondelet
Benoit
B
Mathieu
Myrielle
M
Havaux
Xavier
X
Lause
Pascale
P
Clercx
Cecile
C
Ketelslegers
Jean-Marie
JM
Naeije
Robert
R
McEntee
Kathleen
K
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D001794:Blood Pressure; D004285:Dogs; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000652:urine; D000072396:Endothelin-Converting Enzymes; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008666:Metalloendopeptidases; D009206:Myocardium / Q000378:metabolism*; D010138:Pacemaker, Artificial; D044022:Receptor, Endothelin A / Q000235:genetics* / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics* / Q000378:metabolism; D012119:Respiration
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes