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

Area of Science:

• Endocrinology and Metabolism
• Cardiovascular Physiology
• Neuropeptide Research

Background:

• Urocortin 1 (Ucn 1) demonstrates cardiorenal benefits in animal models of heart failure (HF).
• Previous human studies showed Ucn 1 affects ACTH, cortisol, ANP, and ghrelin in healthy subjects.
• The effects of Ucn 1 in human HF patients remained largely unexplored.

Purpose of the Study:

• To investigate the impact of Ucn 1 infusion on pituitary, adrenal, and cardiovascular systems in human HF.
• To assess if Ucn 1 augments corticotropin and cortisol release in HF patients.
• To evaluate Ucn 1's potential to suppress ghrelin and influence cardiorenal parameters in HF.

Main Methods:

• Eight male volunteers with stable HF (NYHA Class II-III, EF <40%) participated in a randomized, placebo-controlled, cross-over study.
• Participants received a 50 microg intravenous Ucn 1 infusion or placebo over 1 hour on two separate occasions.
• Neurohormones, hemodynamics, and urine indices were measured during a controlled metabolic diet.

Main Results:

• Ucn 1 infusion significantly increased plasma Ucn 1, corticotropin, and cortisol levels compared to placebo.
• The plasma Ucn 1 half-life was determined to be 54+/-3 minutes.
• No significant changes were observed in atrial natriuretic peptide (ANP), ghrelin, hemodynamic parameters, or renal function.

Conclusions:

• A single intravenous infusion of 50 microg Ucn 1 stimulates corticotropin and cortisol release in male patients with stable HF.
• Ucn 1 did not elicit the expected cardiorenal effects or ghrelin suppression in this HF cohort.
• Further research is needed to understand the therapeutic potential and mechanisms of Ucn 1 in cardiovascular disease.