Abstract
The cardiac protective role of a novel erythrocyte-derived depressing factor (EDDF) on spontaneous hypertensive rats (SHR), calcium overload (CaO) rats and Wistar rats and its mechanism was evaluated. Mean artery pressure (MAP), heart rate (HR) and LVdp/dtmax were measured by physiological recorder. The effect of EDDF on the Ca2+-ATPase activity in myocardial sarcoplasmic reticulum (SR) of CaO rats was determined by inorganic phosphate assay. Calcium transport in myocytes was measured by45Ca2+ radioactive isotope measurement. The phosphorylation levels of extracellular signal-regulated protein kinases (ERK1/2) in myocardial tissue of SHR and CaO rats were measured by Western blot method. And the ultrastructures of cardiac muscle cells were observed with the transmission electron microscope. The results indicated that EDDF could significantly decrease MAP, HR and LVdp/dtmax in a dose dependent manner (P < 0.05). It seems that the mechanism might relate with activating the Ca2+-APTase, enhancing the uptake and release of Ca2+ from SR (P<0.05), decreasing the phosphorylation levels of ERK1/2 of myocytes (P < 0.01) and lightening the ultrastructural lesion of cardiac muscle cells. In CaO rats, the Ca2+-ATPase activity decreased clearly compared to control (64.99±7.16 vs 94.48±7.68 nmol · min−1 · mg−1 protein,P < 0.01), while EDDF (100 μg/mL) could significantly increase the activity (87.93 ± 9.54 vs 64.99 ± 7.16,P < 0.05,n = 7). Both uptake and release rate of Ca2+ (μmol45Ca2+/g protein/min) from myocardial SR of CaO rats remarkably decreased compared to control (32.40 ± 2.70 and 15.46 ± 1.49 vs 61.09 ± 10.89 and 25.47 ± 4.29,P < 0.05); EDDF (100 (μg/mL) could significantly stimulate their activities (50.48 ± 6.76 and 21.76 ± 2.75 vs 32.40 ± 2.70 and 15.46 ± 1.49,P < 0.05). EDDF could evidently down-regulate the phosphorylation of ERK1/2 in myocardial tissue from SHR and CaO rats (P < 0.01), lighten the ultrastructural lesion of cardiac muscle cells of SHR as well. It is concluded that EDDF seems to play protective roles on both structure and function of heart, which closely related with amelioration of Ca2+ transport and inhibition of Ca2+-MAP kinase pathway.
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References
Wen, Y. Y., Vascular alteration and their mechanisms in hypertension, in The Vascular Biology (eds. Han, Q.D., Wen, Y.Y.) (in Chinese), Beijing: Union Publishing House of Beijing Medical University and Peking Union Medical College, 1997, 213–223.
Wen, Y. Y., Several new endogenous blood pressure regulation substances, in The Hypertension (eds. Lu, L.S.) (in Chinese), Beijing: The People’s Health Publishing House, 2001, 350–359.
Wen, Y. Y., Zhang, X. C., Xu, X. R. et al., Changes of handling of calcium in mesenteric vascular smooth muscle cells of calcium overload rat, Acta Academiae Medicinae Sinicae (in Chinese), 2000, 22(3): 250–253.
Pang, H., Wen, Y. Y., Shi, L. et al., Protective role of a novel human erythrocyte-derived depressing factor on blood pressure in rats, Chin. Sci. Bull., 2002, 47(9): 717–721.
Lu, T., Wen, Y. Y., Chen, M. Q., The action mechanism of vasodilation of erythrocyte antihypertensive factor, Chin. J. Applied Physiol. (in Chinese), 1994, 1: 5–8.
Wan, F., Wen, Y. Y., The vasodilation mechanism on a novel human erythrocyte-derived depressing factor, Natl. Med. J. China, (in Chinese), 2002, 82(3): 194–197.
Wen, Y. Y., Zhang, X. C., Xu, X. R., Action mechanisms of a new erythrocyte-derived depressing factor, Chin. Sci. Bull., 2000, 45(23): 2113–2118.
Alkinson, J., Poitdeven, P., Mchillon, J. et al., Vascular Ca overload produced by vitamin D3 plus nicotine diminishes arterial distensibility in rats, Am. J. Physiol., 1994, 266(2pt2): H540-H547.
Afzal, N., Dhall, N. S., Differential changed in left and right ventricular SR calcium transport in congestive heart failure, Am. J. Physiol., 1992, 262(3pt2): H868–874.
Bradford, M. M., A rapid sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem., 1976, 72: 248–254.
Jones, C. R., Besch, H. R., Fleming, J. W. et al., Separation of vesicles of cardiac sarcoplasma from vesicles of sarcoplasmic reticulum, J. Biol. Chem., 1979, 254: 530–539.
Osada, M., Netticadan, T., Tamura, K. et al., Modification of ischemia reperfusion induced changes in cardiac sarcoplasmic reticulum by preconditioning, Am. J. Physiol., 1998, 274(2pt): H2025-H2034.
Kirchberger, M., Wong, D., Calcium efflux from isolated cardiac sarcoplasmic reticulum, J. Biol. Chem., 1978, 253: 6941–6945.
Ren, J., Wen, Y. Y., Influence of hypertension on cardiac contractile response of human erythrocyte-derived depressing factor in ventricular myocytes, J. Hypertens., 2003, 21(6): 1183–1190.
Carvajal, K., Hafidi, M., Banos, G., Myocardial damage due to ischemia and reperfusion in hypertriglyceridemic and hypertensive rats: participation of free radicals and calcium overload, J. of Hypertens., 1999, 30: 1038–1043.
Tatchum, T. R., Niederhiffer, N., Amin, F. et al., Aortic stiffness and left ventricular mass in a rat model of isolated systolic hypertension, Hypertension, 1995, 26(6ptl): 963–970.
Qi, Y. F., Dong, L. W., Xue, L. et al., Function changes of myocardial sarcoplamic reticulum induced by vitamin D3 in calcium overload rats, Chin. J. of Patho. Physio. (in Chinese), 2001, 17(2): 289–292.
Langan, E. M., Youkey, J. R., Elmore, J. R. et al. Regulation of MAP kinase activity by growth stimuli in vascular smooth muscle, J. Surg. Res., 1994, 57(1): 215–220.
Guyton, K. Z., Liu, Y., Gorospe, M. et al., Activation of mitogen-activated protein kinase by H2O2, role in cell survival following oxidant injury, J. Biol. Chem., 1996, 271: 4138–4142.
Force, T., Bonventre, J. V., Growth factors and mitogen activated protein kinases, Hypertension, 1998, 31(Pt2): 152–161.
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Wang, Y., Wen, Y., Ma, N. et al. Cardiac protective role of a novel erythrocyte-derived depressing factor on rats and its Ca2+ mechanism. Chin. Sci. Bull. 48, 2710–2714 (2003). https://doi.org/10.1007/BF02901761
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DOI: https://doi.org/10.1007/BF02901761