Objective: To study the effect of human urotensin II (HU II) on secretion of adrenomedullin (ADM) from human vascular endothelial cells (HVEC) and its mechanism.
Methods: In cultured HVEC, different concentrations of HUII were used to stimulate the ADM secretion from HVEC, and the inhibitors of different signal transduction pathway were used to investigate their effects on ADM secretion. The contents of ADM in medium were determined by radio immunoassay.
Results: HUII stimulated secretion of ADM from HVEC in a time-dependent and concentration-dependent manner. The contents of ADM in the experiment groups were changed compared with that in control group (P < 0.05). The increase of ADM could be inhibited by inhibitor of extracellular signal-regulated protein kinase (PD(98059)), inhibitor of P38 kinase (SB(202190)), inhibitor of calmodulin (W(7)) and inhibitor of Ca(2+) (nicardipine) (P < 0.05). The inhibition ratio in those groups was 68%, 78%, 24% and 25% respectively. But the inhibitor of Calcineurin (CaN) and inhibitor of protein kinase C (H(7)) had no influence on the secretion of ADM from HVEC (P > 0.05).
Conclusion: The stimulated effect of HUII on the ADM secretion from HVEC may be mediated by Ca(2+), ERKs, CaM-PK and P38 signal transduction pathways.