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

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.