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?

J Psychosom Res. 2006 Oct;61(4):453-60. doi: 10.1016/j.jpsychores.2006.07.001.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / physiopathology
  • Coronary Vessels / metabolism
  • Coronary Vessels / physiopathology
  • Corticotropin-Releasing Hormone / metabolism*
  • Corticotropin-Releasing Hormone / pharmacology*
  • DNA Primers / genetics
  • Endothelin-1 / metabolism*
  • Endothelium, Vascular / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Nitric Oxide / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology*


  • CRF receptor type 2
  • DNA Primers
  • Endothelin-1
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • Nitric Oxide
  • Corticotropin-Releasing Hormone