CARDIAC INOTROPIC ACTIONS OF UROCORTIN IN CONSCIOUS SHEEP

Urocortin (Ucn) is a recently isolated peptide related to the corticot ropin-releasing factor (CRF) family, which can produce hemodynamic and hormonal actions in conscious rats. This study examined in detail the cardiovascular actions of Ucn and CRF after intravenous injection in chronically instrumented, conscious sheep. Injection of Ucn produced d ose-dependent changes in cardiac contractility [rate of increase of ao rtic flow (dF/dt)], maximum aortic flow (F-max), mean arterial pressur e (MAP), heart rate (HR), cardiac output (CO), and coronary blood flow (CF). Ucn injected at 100 mu g produced a potent increase in dF/dt, f rom 909 +/- 44 to a maximum of 1,849 +/- 901.min(-1).s(-1), and in F-m ax, from 25.5 +/- 0.8 to 36.6 +/- 1.4 l/min. Cardiac contractility inc reased within 30 min of injection and remained significantly elevated for up to 24 h. MAP increased from 78 +/- 2 to 90 +/- 3 mmHg, and HR i ncreased from 73 +/- 4 to 103 +/- 9 beats/min. CO rose from 5.0 +/- 0. 1 to 5.8 +/- 0.2 l/min, whereas central venous pressure, total periphe ral conductance, and stroke volume were unchanged. All Ucn-induced car diovascular effects were inhibited by prior treatment with the CRF ant agonist a-helical CRF-(9-41). Equimolar doses of CRF produced little c hange in any hemodynamic parameter. Both peptides increased plasma lev els of adrenocorticotropin and cortisol, with Ucn having a more potent effect than CRF. We have shown for the first time that Ucn can produc e potent and long-lasting actions to elevate cardiac contractility in conscious animals.