Effect of urocortin 1 infusion in humans with stable congestive cardiac failure

In sheep with HF (heart failure), Ucn1 (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 Ucn1 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 Ucn1 on pituitary, adrenal and cardiovascular systems in the first Ucn1 infusion study in human HF. In human HF, it is proposed that Ucn1 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 μg of Ucn1 or placebo intravenously over 1 h in a randomized time-matched cross-over design. Neurohormones, haemodynamics and urine indices were recorded. Ucn1 infusion increased plasma Ucn1, 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 Ucn1 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 μg of Ucn1 stimulates corticotropin and cortisol in male volunteers with stable HF.