Effect of urocortin 1 infusion in humans with stable congestive cardiac failure.
In sheep with HF (heart failure), Ucn 1 (urocortin 1) decreases total peripheral resistance and left atrial pressure, and increases cardiac output in association with attenuation of vasopressor hormone systems and enhancement of renal function. In a previous study, we demonstrated in the first human studies that infusion of Ucn 1 elevates corticotropin ('ACTH'), cortisol and ANP (atrial natriuretic peptide), and suppresses the hunger-inducing hormone ghrelin in normal subjects. In the present study, we examined the effects of Ucn 1 on pituitary, adrenal and cardiovascular systems in the first Ucn 1 infusion study in human HF. In human HF, it is proposed that Ucn 1 would augment corticotropin and cortisol release, suppress ghrelin and reproduce the cardiorenal effects seen in animals with HF. On day 3 of a controlled metabolic diet, we studied eight male volunteers with stable HF (ejection fraction <40%; New York Heart Association Class II-III) on two occasions, 2 weeks apart, receiving 50 microg of Ucn 1 or placebo intravenously over 1 h in a randomized time-matched cross-over design. Neurohormones, haemodynamics and urine indices were recorded. Ucn 1 infusion increased plasma Ucn 1, corticotropin (baseline, 5.9+/-0.9 pmol/l; and peak, 7.2+/-1.0 pmol/l) and cortisol (baseline, 285+/-42 pmol/l; and peak, 310+/-41 pmol/l) compared with controls (P<0.001, 0.008 and 0.047 respectively). The plasma Ucn 1 half-life was 54+/-3 min. ANP and ghrelin were unchanged, and no haemodynamic or renal effects were seen. In conclusion, a brief intravenous infusion of 50 microg of Ucn 1 stimulates corticotropin and cortisol in male volunteers with stable HF.
Davis
Mark E
ME
Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch 8001, New Zealand. mark.davis@chmeds.ac.nz
Pemberton
Christopher J
CJ
Yandle
Timothy G
TG
Lainchbury
John G
JG
Rademaker
Miriam T
MT
Nicholls
M Gary
MG
Frampton
Christopher M
CM
Richards
A Mark
AM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D006207:Half-Life; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D054832:Urocortins
D054832:Urocortins; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone