Tetrandrine Vasodilation And Myocardial Protection Pharmacological Effects

The major functions of tetrandrine are inhibition of arrhythmia, lowering blood pressure, inhibition of fibrosis and collagen proliferation, anti-tumor, anti-inflammatory and immunoinhibition, lowering blood sugar. Therefore tetrandrine is commonly used for protection against cardiovascular disease, fibrosis of livers and lungs, and so on. Until now, there are many investigations detailing the important roles of endothelium cells, ion channels and adrenoceptors in vasodilatation, as well as the relationship between myocardial infarction and antioxidation, inflammation and apoptosis.In this thesis, the vaso-relaxation effect of tetrandrine is first investigated. And its mechanisms are studied from various aspects, like endothelium cells, calcium channels, potassium channels,α-adrenoceptors andβ-adrenoceptors. Then, a rat model of acute myocardial injury induced by isoproterenol was adopted to evaluate the underlying cardioprotective effect and mechanisms of tetrandrine.The results showed that tetrandrine could endothelium-independently dilate vascular smooth muscle by virtue of its Ca²⁺-antagonistic, K_ATP-open andα₁-adrenoceptor-antagonistic actions. Besides, tetrandrine had prominent cardioprotective effect on current acute myocardial injury model. It could up-regulate the levels of SOD, CAT and GSH in hearts and livers. For the gene expression of GSH-Px, COX-2, Bcl-2 and Bax in left ventricles, tetrandrine prevented the down-regulation of GSH-Px and Bcl-2 levels and the up-regulation of COX-2 and Bax levels. Similar results were obtained from the Western Blot analysis, which indicated the cardioprotective function of tetrandrine may result from antioxidation, anti-inflammatory and anti-apoptosis activities.At last, we attempted to evaluate a possible correlation of the anti-oxidative activities (using the cell-free DPPH assay) and the vaso-relaxation effects (using rat isolated thoracic aorta) of 6 active constituents of traditional Chinese medicine, including baicalin, ligustrazine, notoginsenoside R₁, rhynchophylline, salidroside and tetrandrine. The results showed that baicalin and tetrandrine have the best effects on vaso-relaxation and the free radical scavenging. A positive correlation (R² = 0.7741, p < 0.001) between the anti-oxidative activity and the vascular relaxation effect of the compounds evaluated was illustrated. Hence, our results demonstrated that compounds isolated from TCM herbs studied in the present study seem to possess unique "dual effects" which are beneficial in treating hypertension. In addition, our results may help to strengthen the wisdom of the uses of herbal medicines in treating different diseases with an overall/holistic approach with diverse mechanisms.