Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure.
OBJECTIVE
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).


RESULTS
Eight sheep received incremental intravenous boli of Ucn3 (10, 50, and 100 microg 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).


CONCLUSIONS
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.
Rademaker
Miriam T
MT
Christchurch Cardioendocrine Research Group, The Christchurch School of Medicine, PO Box 4345, Christchurch 8001, New Zealand. miriam.rademaker@chmeds.ac.nz
Cameron
Vicky A
VA
Charles
Chris J
CJ
Richards
A Mark
AM
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004573:Electrolytes / Q000097:blood / Q000652:urine; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006400:Hematocrit; D006728:Hormones / Q000378:metabolism*; D012756:Sheep; D054832:Urocortins; D014655:Vascular Resistance / Q000187:drug effects
D004573:Electrolytes; D006728:Hormones; C426704:UCN3 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone