Effects of beta-endorphin on endothelial/monocytic endothelin-1 and nitric oxide release mediated by mu1-opioid receptors: a potential link between stress and endothelial dysfunction?

Abstract

Observations have been made linking the presence of psychosocial factors associated with elevated beta-endorphin concentrations with atherosclerosis. In this study, the authors assume an important role of the stress hormone beta-endorphin in several mechanisms that contribute to a dysbalance of human endothelial and monocytic endothelin (ET)-1 and nitric oxide (NO) release, mediated by mu1-opioid receptors. ET-1 and NO release were quantified via enzyme-linked immunosorbent assay (ELISA) or fluorometrically. mu1-Opioid receptors were identified by polymerase chain reaction (PCR) after stimulation with beta-endorphin. beta-Endorphin significantly increased endothelial and monocytic ET-1 release. The effect was mediated by mu1-opioid receptors and abolished by naloxonazine, a selective mu1-opioid receptor antagonist. In contrast, NO release was decreased under the influence of beta-endorphin. mu1-Opioid receptors on human monocytes and endothelial cells mediated a beta-endorphin-induced stimulation of ET-1 release, whereas NO release was decreased. Thus, the authors hypothesize a role of beta-Endorphin in the pathogenesis of stress-induced endothelial dysfunction through peripherally circulating beta-endorphin, which may offset the balance of vasoactive mediators, leading to an unopposed vasoconstriction. The data may also provide a new concept of mu1-opioid receptor antagonists, preventing beta-endorphin-induced disorders of vascular biology.