Bin Geng, Fen Qi Yong, Hua Liu Xiu, Hong Zhang Bao, Zheng Pang Yong, Shu Tang Chao
Institute of Cardiovascular Research, Peking University First Hospital, Beijing, 100034, China.
Life Sci. 2005 Jul 15;77(9):966-79. doi: 10.1016/j.lfs.2004.12.037. Epub 2005 Apr 18.
We investigated the relationship between cardiac dysfunction and Ca2+ transport in the myocardial sarcoplasmic reticulum (SR) during the pathogenesis of cardiovascular calcification in rats. The possible mechanism of SR dysfunction was explored by detecting the alteration of the nitric oxide/nitric oxide synthase (NO/NOS) pathway in the SR. Using the vitamin D plus nicotine (VDN treatment for 2 week and 6 week) experimental model of cardiac calcification, cardiac function and sarcoplasmic reticulum function were measured. Inhibition of cardiac functions in vivo (peak rate of contraction and peak rate of relaxation, P < 0.05 or P < 0.01) were observed in all calcification groups, simultaneously, Ca2+ release and uptake in the SR as well as the Ca2+ release channel and Ca2+ pump activity were inhibited. Myocardial Ca2+ concentration and cardiac and SR dysfunction were inversely related (P < 0.05). The specific NO/NOS pathway (NO production, NOS activity and nNOS expression in the SR) was upregulated in the SR and associated with calcification (both 2- and 6 week VDN groups). These results indicate that cardiac dysfunction associated with myocardial calcification might be mediated by SR dysfunction, which may result from an impaired SR-specific NO/NOS pathway.
我们研究了大鼠心血管钙化发病过程中心脏功能障碍与心肌肌浆网（SR）中Ca2+转运之间的关系。通过检测SR中一氧化氮/一氧化氮合酶（NO/NOS）途径的变化，探讨了SR功能障碍的可能机制。采用维生素D加尼古丁（VDN处理2周和6周）的心脏钙化实验模型，测量心脏功能和肌浆网功能。在所有钙化组中均观察到体内心脏功能受到抑制（收缩峰值速率和舒张峰值速率，P<0.05或P<0.01），同时，SR中的Ca2+释放和摄取以及Ca2+释放通道和Ca2+泵活性均受到抑制。心肌Ca2+浓度与心脏和SR功能障碍呈负相关（P<0.05）。SR中特定的NO/NOS途径（SR中的NO产生、NOS活性和nNOS表达）上调，且与钙化相关（2周和6周VDN组均如此）。这些结果表明，与心肌钙化相关的心脏功能障碍可能由SR功能障碍介导，而SR功能障碍可能源于SR特异性NO/NOS途径受损。
