Cardiovascular effects of urocortin 2 and urocortin 3 in patients with chronic heart failure

Br J Clin Pharmacol. 2016 Oct;82(4):974-82. doi: 10.1111/bcp.13033. Epub 2016 Jul 28.

Abstract

Aims: Urocortin 2 and urocortin 3 may play a role in the pathophysiology of heart failure and are emerging therapeutic targets. We aimed to examine the local and systemic cardiovascular effects of urocortin 2 and urocortin 3 in healthy subjects and patients with heart failure.

Methods: Patients with heart failure (n = 8) and age and gender-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of urocortin 2 (3.6-36 pmol min(-1) ), urocortin 3 (360-3600 pmol min(-1) ) and substance P (2-8 pmol min(-1) ). Heart failure patients (n = 9) and healthy subjects (n = 7) underwent non-invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (573-5730 pmol kg(-1) min(-1) ), urocortin 2 (36-360 pmol min(-1) ), urocortin 3 (1.2-12 nmol min(-1) ) and saline placebo.

Results: Urocortin 2, urocortin 3 and substance P induced dose-dependent forearm arterial vasodilatation in both groups (P < 0.05 for both) with no difference in magnitude of vasodilatation between patients and healthy subjects. During systemic intravenous infusions, urocortin 3 increased heart rate and cardiac index and reduced mean arterial pressure and peripheral vascular resistance index in both groups (P < 0.01 for all). Urocortin 2 produced similar responses to urocortin 3, although increases in cardiac index and heart rate were only significant in heart failure (P < 0.05) and healthy subjects (P < 0.001), respectively.

Conclusion: Urocortins 2 and 3 cause vasodilatation, reduce peripheral vascular resistance and increase cardiac output in both health and disease. These data provide further evidence to suggest that urocortins 2 and 3 continue to hold promise for the treatment of heart failure.

Keywords: cardiac; heart failure; inotrope; urocortin; vasodilator.

Publication types

  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Cardiography, Impedance
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Forearm / blood supply
  • Forearm / physiology*
  • Heart Failure / physiopathology*
  • Heart Rate / drug effects
  • Humans
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Nitroprusside / pharmacology
  • Plethysmography
  • Regional Blood Flow / drug effects*
  • Substance P / pharmacology
  • Urocortins / administration & dosage
  • Urocortins / pharmacology*
  • Vascular Resistance / drug effects
  • Vasodilation / drug effects

Substances

  • UCN2 protein, human
  • UCN3 protein, human
  • Urocortins
  • Nitroprusside
  • Substance P
  • Corticotropin-Releasing Hormone