Studies On The Effects Of Anti-hypertension Of Ditaurate Magnesium Coordination Compound In Vivo And Vitro

Objective: To observe the anti-hypertension effects of ditaurate magnesium coordination compound (DTMCC) on L-NNA induced hypertensive rats, study the effects of DTMCC against aorta contraction of rabbit which induced by noradrenaline (NA) and KC1 in vitro and explore the feasible mechanism of anti-hypertension effects. Methods:1. In vivo: L-NNA(15mg/kg), a NOS inhibiter, was administrated intraperitoneally for 4 weeks to establish hypertension model in rats. DTMCC 5, 15, 30mg/kg, taurine (TAU) 25.69mg/kg, magnesium sulfate (MgSO₄) 25.30mg/kg were administrated intraperitoneally for 4 weeks. After 4 weeks of treatment the effects of drugs on blood pressure, heart weight/body weight(HW/BW), endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in plasma were observed and determined.2. In vitro: Put the aorta strip of rabbit into the bath which is filled with Kersh solution and mixed gas (95%O₂+5%CO₂). Make the tension of aorta strip rising after adding NA(1 × 10^-6mol/L) and KCl (30mmol/L) into the bath after 60 min stabilized period, then put different doses of DTMCC (20,10 and 7 mg/ml), TAU (17.13mg/ml) and MgSO₄ (16.86mg/ml) into it respectively, and the tension inhibition ratio (%) of aorta strip were observed and determined.Results:1. In vivo: After 4 weeks of treatment the MAP for DTMCC-H, DTMCC-M, DTMCC-L, L-NNA were 121.13±3.68, 130.13±4.38, 126.07±2.23, 140.87±4.16 mmHg, (P<0.05 vs L-NNA), respectively. MAP for DTMCC-H is significantlydifferent with MgSO4 (128.82±3.52 mmHg) and TAU (129.94±5.73 mmHg, P<0.05). Data of each group of HW/BW are significant with L-NNA group (P<0.05). Compared with L-NNA group(123.43±6.08 pg/ml), DTMCC-L(112.00±5.46 pg/ml)and TAU (95.12±5.36 pg/ml)can significantly inhibit ET-1 level of blood plasma (P<0.05), and CGRP level is significantly raised in DTMCC-L (34.29±9.54 pg/ml) and MgSO4 (31.47±3.75 pg/ml) compared with L-NNA group(23.59±2.40 pg/ml, P<0.05).2. In vitro: Each group of DTMCC can inhibit the contractive action of aorta strip induced by NA and show a dose-dependent relationship, DTMCC-L was 12.79±3.82%, DTMCC-M 24.41±2.02%, DTMCC-H 75.34±3.57%. And the action of DTMCC-H is significantly different with MgSO4 (67.99±3.75%)and TAU ( 44.36±4.10%, P<0.05).DTMCC can inhibit the contractive action of aorta strip induced by KCl, the action of DTMCC-H is significantly different with MgSO4 and TAU (P<0.05). DTMCC-L was 6.07±l.05%, DTMCC-M 34.88±3.15%, DTMCC-H 63.63±3.84%, MgSO4 55.96±4.03%, TAU 48.80±3.55%. A dose-dependent relationship existed.Conclusion: DTMCC show strong anti-hypertension effect, and it can partly protect heart based on HW/BW data. Also DTMCC can significantly depress the contractive action of aorta strip induced by NA and KCl, and a dose-dependent relationship existed.