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Cardiovascular effects of urocortin 2 and urocortin 3 in patients with chronic heart failure
Author(s) -
Stirrat Colin G.,
Venkatasubramanian Sowmya,
Pawade Tania,
Mitchell Andrew J.,
Shah Anoop S.,
Lang Ninian N.,
Newby David E.
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13033
Subject(s) - urocortin , heart failure , medicine , pharmacology , endocrinology , receptor
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.