[Effect of tanshinone II A on angiotensin receptor in hypertrophic myocardium of rats with pressure over-loading].

OBJECTIVE: To explore the molecular biological mechanism of tanshinone II A (TSN) in preventing hypertensive left ventricular hypertrophy (HLVH) through studying the effects of TSN on angiotensin receptor (ATR) expression and free calcium ion ([Ca2+]i) in rats with hypertrophic myocardium caused by abdominal aorta constriction. METHODS: SD rats were established into HLVH model by abdominal aorta constriction operation, they were randomly divided into the model group, the three treated groups treated respectively with intra peritoneal injection of low dose TSN (10 mg/kg) and high dose TSN (20 mg/kg) and gastrogavage of Valsartan (10 mg/kg) once a day 4 weeks after modeling. Besides, 8 sham-operated SD rats were set up as the control group. Eight weeks later, rats' caudal arterial pressure was measured, and their hearts were taken for measuring the left ventricular mass index (LVMI) and myocardial fiber diameter (MFD) by HE stain of the pathological section. Moreover, the mRNA and protein expressions of AT1 and AT2 receptors in the left ventricular tissue were detected by RT-PCR and Western blot, and [Ca2+]i concentration was determined with laser-scanning confocal microscope. RESULTS: (1) The elevated blood pressure in the TSN treated groups, either high or low dose, remained unchanged, significantly higher than that in the control group and the Valsartan treated group (P < 0.01, P < 0.05). (2) LVMI and MFD in the three treated groups were significantly lower than those in the model group (P <0.01), respectively, although they were higher than those in the control group (P <0.05). (3) The mRNA and protein expressions of AT1 receptor were obviously lower in the three treated groups than those in the model groups (P < 0.05); but the lowering was more significant in the valsartan treated group (P < 0.05). (4) The mRNA and protein expressions of AT2 receptor were significantly higher in the Valsartan treated group as compared with other groups (P < 0.05), while the difference among the other groups showed no statistical significance (P > 0.05). (5) The elevated (Ca2+]i concentration in hypertrophic myocardium after modeling was significantly lowered after treatment in the three treated groups (P < 0.05), but the lowering in the high TSN treated group was more significant than that in the Valsartan treated group (P <0.05). CONCLUSION: The inhibition of TSN on myocardial hypertrophy is blood pressure independent, its mechanism is possibly related with the inhibition on AT1R gene expression and the blocking of free calcium ion influx in cardiac muscle cells. AT2 receptor may participate the effect of Valsartan in lowering blood pressure and reversing myocardial hypertrophy.