Modulation of Carvedilol on Cardiac Calcium-handling Protein Expression Level: Canine Model of Rapid Ventricular Pacing

• Main Authors: Yi-Fan Yang, 楊怡凡
• Other Authors: Ming-Jai Su
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/33508678635021439360

碩士 === 國立臺灣大學 === 藥理學研究所 === 88 === Besides the well-known vasodilating a- and b-blocking activity for hypertension treatment, carvedilol has been proved to use in the treatment of congestive heart failure. However, the novel properties of carvedilol that may function to protect the heart from chronic pathological processes are still poorly understood. In cardiac muscle, sarcoplasmic reticulum (SR) plays a central role in intracellular Ca2+ concentration regulation. To characterize the effect of carvedilol on the gene expression of calcium-handling proteins of SR in cardiac muscle, we established tachycardia-induced heart failure model of dogs in the present study. We estimated the contractile function of isolated cardiac muscle strips and detected the calsequestrin, L-type Ca2+-channel, Na+-Ca2+ exchanger, phospholamban, ryanodine receptor, and SR Ca2+-ATPase mRNA expression level by RT-PCR and competitive RT-PCR techniques. We also detected the SR Ca2+-ATPase protein expression level by Western blotting techniques. The results of our studies showed that the SR function was suppressed obviously in the tachycardia-induced heart failure tissue. We also found that the SR Ca2+-ATPase mRNA expression level was decreased, but the Na+-Ca2+ exchanger and the phospholamban mRNA expression level were increased in the failing heart. Although carvedilol did not significantly improve the haemodynamic changes of tachycardia-induced heart failure in our dog model, it reduced the change of the mRNA expression level of SR Ca2+-ATPase, Na+-Ca2+ exchanger and phospholamban in the dog hearts with rapid-paced. Though mRNA expression level of SR Ca2+-ATPase in cardiac tissue of rapid-pacing dogs was up-regulate by carvedilol treatment, the protein expression level of SR Ca2+-ATPase was not increased symmetrically. The mechanism responsible for the up-regulation of SR Ca2+-ATPase mRNA by carvedilol is still unclear. Further studies are needed.