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.

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.

Keywords: Corticotropin-releasing hormone, Endothelial dysfunction, Endothelin-1, NO