As U50488H was administered, SERCA2a was upregulated, the calcium-regulated proteins were activated, leading to CaMKII inhibition and CREB phosphorylation; meanwhile, the expression of ERS regulatory proteins showing ERS injury was also alleviated, suggesting that κ-OR agonist can inhibit ERS through activating Ca2+-SERCA2a in HF rats. Here, CREB1 is linked to hydrops fetalis.