European Heart Journal Advance Access published online on July 6, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl138
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1 Christchurch Cardioendocrine Research Group, The Christchurch School of Medicine, PO Box 4345, Christchurch 8001, New Zealand
* To whom correspondence should be addressed. Aims To investigate the haemodynamic, hormonal, and renal effects of peripheral urocortin 3 (Ucn3) administration for the first time in either normal health or heart failure (HF). Methods and results Eight sheep received incremental intravenous boli of Ucn3 (10, 50, and 100 µg at 2-h intervals) before (normal) and during pacing-induced HF. Compared with controls, Ucn3 induced immediate, dose-dependent increases in cardiac output (normal 4.21 ± 0.23 vs. 5.65 ± 0.32 L/min, P < 0.001; HF 2.20 ± 0.14 vs. 4.43 ± 0.31 L/min, P < 0.001) and decreases in peripheral resistance (normal 20.8 ± 1.0 vs. 16.2 ± 0.8 mmHg/L/min, P < 0.01; HF 34.4 ± 1.7 vs. 16.2 ± 0.5 mmHg/L/min, P < 0.001) and left atrial pressure (normal 4.5 ± 0.3 vs. 0.6 ± 0.2 mmHg, P < 0.001; HF 23.0 ± 0.6 vs. 5.8 ± 1.9 mmHg/L/min, P < 0.001). Arterial pressure was minimally elevated in normals (P < 0.001) and reduced in HF (P < 0.05). In HF only, Ucn3 decreased plasma vasopressin (3.33 ± 0.36 vs. 1.73 ± 0.21 pmol/L, P < 0.05), endothelin-1 (3.56 ± 0.28 vs. 2.64 ± 0.24 pmol/L, P < 0.001), renin (2.74 ± 1.17 vs. 1.04 ± 0.22 nmol/L/h, P < 0.001), aldosterone (1494 ± 400 vs. 726 ± 168 pmol/L, P < 0.05), and epinephrine (1608 ± 278 vs. 1039 ± 75 pmol/L, P < 0.05), and increased urine output (P < 0.05), sodium excretion (P < 0.01), and creatinine clearance (P < 0.05). Conclusion Ucn3 has significant cardiovascular effects in normal and HF sheep, supporting a role for this peptide in circulatory regulation. In HF, more prominent haemodynamic changes were associated with beneficial endocrine and renal effects, suggesting Ucn3 has therapeutic potential in this disease.
Received March 23, 2006
Revised June 8, 2006
Accepted June 15, 2006
Preclinical research
Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure
Miriam T. Rademaker 1 *,
Vicky A. Cameron 1,
Chris J. Charles 1,
and
A. Mark Richards 1
Miriam T. Rademaker, E-mail: miriam.rademaker{at}chmeds.ac.nz
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