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



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.



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.



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.
British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. colin.stirrat@ed.ac.uk.
Colin G
CG
Stirrat
British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Sowmya
S
Venkatasubramanian
British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Tania
T
Pawade
British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Andrew J
AJ
Mitchell
British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Anoop S
AS
Shah
British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Ninian N
NN
Lang
British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
David E
DE
Newby
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002307:Cardiography, Impedance; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D054832:Urocortins / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
C426705:UCN2 protein, human; C426704:UCN3 protein, human; D054832:Urocortins; D009599:Nitroprusside; D013373:Substance P; D003346:Corticotropin-Releasing Hormone
cardiac; heart failure; inotrope; urocortin; vasodilator