Divergent effects of corticotropin releasing hormone on endothelial cell nitric oxide synthase are associated with different expression of CRH type 1and 2 receptors

1 Endothelium is a target for an array of factors involved in inflammation. Endothelial cells express receptors for CRH, a neuropeptide produced durin g inflammation. We report both the concentration-dependent inhibitory effec t of CRH upon cytokine-stimulated nitrite release by H5V murine endotheliom a cells, and its stimulatory one in HUVEC cells. 2 Western blot analysis showed that CRH inhibits cytokine-stimulated iNOS p rotein in H5V cells, and, instead, potentiated it in HUVEC cells. 3 H5V cells expressed both CRH receptors (CRH-R1 and R2) mRNAs, whereas HUV EC cells expressed the CRH-R2 mRNA solely. 4 CRH increased medium nitrites and iNOS protein expression in H5V cells pr etreated with the selective CRH-R1 antagonist CP 154,526. However, the sele ctive CRH-R2 antagonist anti-Svg-30 failed to produce similar effects. In f act, anti-Svg-30 inhibited CRH-induced increase of nitrite release and iNOS expression in HUVEC cells. 5 Our results confirm the activating role of CRH on endothelial cells, alth ough it suggests its possible inhibitory role in the late phase of the infl ammatory response. NO-mediated effects of CRH on endothelial cells could be exploited in therapeutic strategies related to inflammatory and/or degener ative diseases.