Cardiovascular Effects of Urocortin 2 and Urocortin 3 in Patients with Chronic Heart Failure

Colin G Stirrat, Sowmya Venkatasubramanian, Tania Pawade, Andrew J Mitchell, Anoop S Shah, Ninian N Lang, David E Newby

Research output: Contribution to journalArticlepeer-review


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 sex-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), urocortin 3 (360-3600 pmol/min) and substance P (2-8 pmol/min). 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/min ), urocortin 2 (36-360 pmol/min ), urocortin 3 (1.2-12 nmol/min) 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.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Early online date8 Jun 2016
Publication statusE-pub ahead of print - 8 Jun 2016


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