The effect of urocortin II administration on the coronary circulation and cardiac function in the anaesthetized pig is nitric-oxide-dependent

We planned to determine the primary effects and mechanisms of urocortin II, a member of the corticotrophin-releasing factor (CRF) family highly expressed in the cardiovascular system, on coronary blood flow and myocardial function in vivo. Urocortin 11 was infused into the left anterior descending coronary artery in 25 anaesthetized pigs whilst measuring haemodynamic variables, coronary blood flow, ventricular dP/dt(max) cardiac output and percentage of segmental shortening. This infusion was repeated after blockade of the autonomic nervous system, nitric-oxide synthase (NOS) or subtype 2 of the CRF receptors. In all experiments changes in heart rate and aortic blood pressure were prevented. Intracoronary urocortin 11 increased, within 60 s, coronary blood flow (15 +/- 3.2%, P<0.05), dP/dt(max) (12.7 +/- 2.6%, P<0.05), cardiac output (16 +/- 2.3%, P<0.05) and percentage of segmental shortening (19.8 +/- 3.8%, P<0.05). Blockade of NOS abolished only the coronary effects whereas blockade of subtype 2 of the CRF receptors abolished all cardiac and coronary effects. It was: shown for the first time that urocortin 11 administration primarily increases coronary blood flow and myocardial function through the release of nitric oxide and activation of subtype 2 of the CRF receptors in the anaesthetized pig. This provides a mechanism through which a local increase of urocortin 11 levels can help improve a compromised cardiovascular function. (C) 2007 Elsevier B.V. All rights reserved.