CRH and Urn2 regulate NO bioavailability, ROS levels and antioxidant defence systems in endothelial cells
Sofia Gougoura1, Panagiotis Liakos1,2 & George Koukoulis1
Corticotropin-releasing hormone (CRH) and Urocortin 2 (Urn2) are secreted locally in peripheral tissues and play a direct immunomodulatory role as endocrine or paracrine mediators of inflammation. Studies on CRH as well as Ucn2 and vascular endothelial cells suggest that CRH may play a pivotal role in the regulation of vascular endothelial function under normal and pathological conditions. The present study was undertaken to determine whether CRH and Urn2 affect the endothelial redox state. Therefore, in macroendothelial EAhy926 cells exposed in vitro to CRH and Urn2 for 2 h, at concentration10−7 M, were measured the intracellular reactive oxygen species (ROS), nitric oxide (NO) and glutathione levels in addition to endothelial nitric oxide synthase (eNOS) and catalase activity, in the presence or absence of selective CRH/Urn2 receptor inhibitors, antalarmin and astresin-2b respectively. CRH acting through both receptors induced a significant increase of intracellular ROS content (P<0.001) and catalase activity (P<0.001) accompanied by a simultaneous significant decrease of eNOS activity and NO levels (P<0.001). Urn 2 acting through CRHR2 receptor induced a significant increase of eNOS and catalase activity (P<0.001) and NO levels (P<0,001) but did not affect considerably the intracellular levels of ROS. Our data indicate that CRH and Urn2 may act as regulators of pro-inflammatory mechanisms inducing adaptation of endothelial cell function to local stress.