Abstract 15716: Urocortin 2 and 3 - Potent and Prolonged Arterial Vasodilatation In Vivo In Man
Background: Urocortin 2 (Ucn 2) and 3 (Ucn 3) are peptide isoforms with comparable cardiovascular effects in animal models that include vasodilatation and inotropism. In an in vivo human forearm arterial model, we assessed the pharmacodynamic profiles of Ucn 2 and Ucn 3.
Methods: Eight healthy male volunteers (mean age 23±4 years) were recruited to a randomized, double-blinded study. On two occasions separated by at least one week, bilateral forearm blood flow was measured by venous occlusion plethysmography during incremental infusions of Ucn 2 (15-500 ng/min) and Ucn 3 (5-150 µg/min). Systemic arterial blood pressure and heart rate were monitored throughout.
Results: Both Ucn 2 and 3 evoked dose-dependent arterial vasodilatation (p <0.0001) without tachyphylaxis. At the highest dose (150 µg/min), Ucn 3 caused a transient tachycardia (p <0.0001) and a decrease in diastolic blood pressure (p= 0.0184) without significant alteration in contralateral forearm arterial blood flow. This phenomenon was not observed in response to Ucn 2 despite similar arterial vasomotor effects. Systolic blood pressure remained unchanged (p=ns) for both Ucn 2 and 3. Maximal vasodilatation was apparent 20 min after infusion of Ucn 2. There was a slow offset of action with blood flow decreasing to 50% of maximal vasodilatation in 50 mins and 30 mins for Ucn 2 and 3 respectively.
Conclusion: Urocortins 2 and 3 cause potent and prolonged peripheral arterial vasodilatation without tachyphylaxis. This peptidic system holds major promise in the treatment of heart failure with important differential effects in these two isoforms.
- © 2011 by American Heart Association, Inc.