title: Effects of corticotropin-releasing hormone (CRH) on endothelin-1 and NO release, mediated by CRH receptor subtype R2: a potential link between stress and endothelial dysfunction?
abstract: OBJECTIVE
  Psychosocial factors, associated with elevated corticotropin releasing hormone (CRH) concentrations, have been reported to be independently associated with coronary heart disease.
  
  
  METHODS
  Endothelin-1 and NO release of human endothelial cells were quantified via ELISA or fluorometrically after treatment with CRH. CRH-receptor subtype 2 (CRH-R2) was visualized on endothelial cells by immunohistochemistry and confirmed by polymerase chain reaction using CRH-R2 primers.
  
  
  RESULTS
  CRH induced a significant increase of ET-1 release, and the effect was abolished by the CRH-receptor antagonist astressin. The effect was mediated by CRH-R2. In contrast, NO release was not affected.
  
  
  CONCLUSIONS
  CRH-R2 is expressed on human endothelial cells, mediating the CRH-induced stimulation of ET-1 release, whereas NO release is not affected. Thus, peripherally circulating CRH may offset the balance between endothelial vasoconstrictor and vasodilator release with unopposed vasoconstriction. Our data may provide a new concept on how CRH-receptor antagonists may prevent CRH-induced disorders of vascular biology.
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, Ludwig-Maximilian-Universität, Munich, Germany. uwilbert@med.uni-muenchen.de
authors.forename: Ute
authors.initials: U
authors.lastname: Wilbert-Lampen
authors.forename: Anja
authors.initials: A
authors.lastname: Trapp
authors.forename: Michaela
authors.initials: M
authors.lastname: Modrzik
authors.forename: Barbara
authors.initials: B
authors.lastname: Fiedler
authors.forename: Florian
authors.initials: F
authors.lastname: Straube
authors.forename: Andrea
authors.initials: A
authors.lastname: Plasse
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*
chemical_list: C101531:CRF receptor type 2; D017931:DNA Primers; D019332:Endothelin-1; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone