Positive Chronotropic And Inotropic Effects By Urocortin And Expression Of CRF-R2β MRNA In The Heart

Urocortin (Ucn), a 40 amino acid peptide, belongs to the corticotropin -releasing factor (CRF) family and displays 45% amino acid sequence homology to CRF. Effects of CRF on the cardiovascular system have been extensively studied. It has been shown that CRF administered into the cerebral ventricles increases the heart rate, cardiac output and mean arterial blood pressure, intravenous administration of CRF, however, decreases the mean arterial blood pressure. CRF plays biological roles by acting on CRF receptors (CRF-R1 and CRF-R2), and CRF-R1 is expressed in brain and pituitary. However, CRF-R2 is expressed not only in the central nervous system but also in peripheral tissues, including the heart. Ucn is reported to bind and activate CRF-R to a greater extent than CRF, and Ucn has much greater affinity for CRF-R2. It is therefore suggested that Ucn may be a nature ligand for CRF-R2, and its cardiovascular effects might be more potent than those of CRF.Ucn administered intravenously to the conscious rats produces a slow and long-lasting decrease in mean arterial blood pressure, which parallels with a rise in heart rate and cardiac output. A significant increase in cardiac contractility was speculated after intravenous administration of Ucn to the sheep as reflected by elevation in both maximal ascending aortic blood flow and ascending aortic dF/dt. However, Ucn injected into the lateral cerebral ventricle in rats increases blood pressure slightly and has no effect in myocardial contractility. A recent study in isolated rat hearts showed a direct evidence of positive inotropic action induced by Ucn. The purpose of this study was to investigate the effects of Ucn on the rat and rabbit right atrium, papillary muscles and rat right ventricle strip, and the effects of Ucn on action potentials of the rat papillary muscles and left atrium. We also compared the...