Experimental Research Of Relationship Between 5-hydroxytriptamine And Pathogenesis Of Cardiac Hypertrophy

In present study, we systemically researched 5-HT effects on cardiovascular system, its concentration and receptor in caidiac tissue, cellular signal transduction, and electrophysiology to discuss the relationship between 5-HT and pathogenesis of cardiac hypertrophy. 1 .Research of relationship between experimental cardiachypertrophy and the concentration of 5-HT in myocardial tissue To study the change of 5-HT in myocardial tissue of rats with cardiac hypertrophy and elucidate the relationship between 5-UT and cardiac hypertrophy. Rats were clipped in aorta and injected thyroxine intraperitoneally to establish pressure overload and endocrine induced cardiac hypertrophy model respectively. Results showed that cardiac hypertrophy appeared significantly in the rats with aorta clipped. In the meantime the concentration of 5-UT increased significantly with the degree of cardiac hypertrophy, showing the positive correlation between them. Similarly, at the second week symptom of cardiac hypertrophy appeared and became significant at the fourth week in the rats injected -7- thyroxine intraperitoneally. In the cardiac tissue, concentration of 5-HT rose markedly when the rats were killed at the second, third and fourth week. In conclusion, 5-IIT may be involved in pathogenesis of myocardial hypertrophy and the further study should be carried to elucidate their relationship. 2. Study of 5-HI receptor in ventricular myocytes by immuno- histochemistry Immunohistochemistry was used to study whether 5-HT receptors express on rat ventricular myocytes and the effect of extraneous 5-HT on 5-HT receptor expression. Results showed there were 5-HT receptors expressing on the membrane of ventricular myocytes. Under normal optical microscope, the positive immunoreaction was showed as brown granules evenly distributing on the membrane. When 5-HT (10 ii mol.JJ?) was added to the culture medium for 48 hours, the immunoreaction increased remarkably, suggesting that extraneous 5-HT could activate the expression of 5-HT receptor. 3. Experimental research of 5-hydroxytryptamine increasing 2+ intracellular free Ca of myocardium Neonatal rat myocardium was cultured to measure intracellular free Ca2~ concentration by using calcium fluorescent probe Fluo-3/AM and laser confocal microscope. 5-HT was found to increase intracellular free Ca2~ concentration in a dose-dependent manner. Addition of the dihydropyridine calcium antagonists, lacidipine, to the cells partially abolished the 5-HT-induced response. Similarly prior addition of ryanodine, an regulator of sarcoplasmic reticulum ryanodine receptor, -8- showed the same action to 5-HT. If extracellular free Ca2~ was chelated by 2+ EGTA, the increase in Ca stimulated by 5-UT was curtailed significantly. Further study showed that cyprohatidine, a 5-HT2R antagonist, also partly diminished the 5-HT-induced response. 5-HT increasing intracellular free Ca2~ may be due to extracellular Ca2~ influx via dihydropyridine calcium channels or 5-HT2R as well as release of Ca2~ from intracellular stores. 4. Effects of 5-hydroxytriptainine on the proliferation and protein kinase C activity in cultured ventricular cells of rats...