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Focuses on the cardiac protective role of novel erythrocyte-derived depressing factor (EDDF) in spontaneous hypertensive rats (SHR), calcium overload (CaO) rats, and Wistar rats. Evaluation of the EDDF mechanism; Measurement of mean artery pressure (MAP), heart rate (HR) and LVdp/dtmax; Use of inorganic phosphate assay to determine the effect of EDDF on the Ca2+-ATPase activity in myocardial sarcoplasmic reticulum (SR) of CaO rats; Use of 45Ca2+ radioactive isotope measurement to determine calcium transport in myocytes; Use of the Western blot method to determine the phosphorylation levels of extracellular signal-regulated protein kinases (ERK1/2) in myocardial tissue of SHR and CaO rats; Observation of the unltrastructures of cardiac muscle cells with the transmission electron microscope; Indication that EDDF can significantly lower MAP, HR and LVdp/dtmax in a dose dependent manner; Effect on the ultrastructural lesion of cardiac muscle cells; Finding that uptake and release rate from myocardial SR and CaO rats significantly decreased compared to the control.