title: Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure.
abstract: 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.
authors.affiliation: Christchurch Cardioendocrine Research Group, The Christchurch School of Medicine, PO Box 4345, Christchurch 8001, New Zealand. miriam.rademaker@chmeds.ac.nz
authors.forename: Miriam T
authors.initials: MT
authors.lastname: Rademaker
authors.forename: Vicky A
authors.initials: VA
authors.lastname: Cameron
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Charles
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: 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
chemical_list: D004573:Electrolytes; D006728:Hormones; C426704:UCN3 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone