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?
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.
Wilbert-Lampen
Ute
U
Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, Ludwig-Maximilian-Universität, Munich, Germany. uwilbert@med.uni-muenchen.de
Trapp
Anja
A
Modrzik
Michaela
M
Fiedler
Barbara
B
Straube
Florian
F
Plasse
Andrea
A
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*
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