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

Stirrat, C. G., Venkatasubramanian, S., Pawade, T., Mitchell, A. J., Shah, A. S., Lang, N. N. and Newby, D. E. (2016) Cardiovascular effects of urocortin 2 and urocortin 3 in patients with chronic heart failure. British Journal of Clinical Pharmacology, 82(4), pp. 974-982. (doi: 10.1111/bcp.13033) (PMID:27275843) (PMCID:PMC5104489)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lang, Dr Ninian
Authors: Stirrat, C. G., Venkatasubramanian, S., Pawade, T., Mitchell, A. J., Shah, A. S., Lang, N. N., and Newby, D. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:British Journal of Clinical Pharmacology
Publisher:Wiley
ISSN:0306-5251
ISSN (Online):1365-2125
Published Online:08 June 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in British Journal of Clinical Pharmacology 82(4):974-982
Publisher Policy:Reproduced under a Creative Commons License

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