Nirwane Abhijit, Pawar Vivek, Majumdar Anuradha
J Complement Integr Med. 2015 Jun;12(2):143-51. doi: 10.1515/jcim-2015-0009.
Effective diet/drug combinations may show additive or synergistic effects in reducing endothelial risk factors vis-à-vis monotherapies. The study evaluated the effect of combined therapy of Telmisartan and omega 3-fatty acids in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats.
Forty-eight male Wistar rats (180-220 g) were randomized into eight groups; control, sodium arsenite (1.5 mg/kg/day) exposed, sodium arsenite exposure followed by treatment with Telmisartan, omega 3-fatty acids, the combination and/or endothelial modulators for 2 weeks depending on the allocated group. VED was assessed by estimating vascular reactivity. Serum thiobarbituric acid-reactive substances (TBARS), nitrite/nitrate levels, reduced glutathione (GSH) levels, superoxide dismutase (SOD) activity, serum cholesterol and triglyceride levels were also determined.
Sodium arsenite produced VED by attenuating acetylcholine-induced endothelial relaxation (% Rmax= 45.36), decreasing levels of serum nitrite/nitrate (9.28 μM/mg protein), GSH (16.06 μg/mg of protein), SOD activity (30.69 units/mg protein) and increasing TBARS (0.19 µM/mg protein) compared with control group. The combined therapy with Telmisartan (10 mg/kg/day) and omega 3-fatty acids (180 mg/kg/day) (% Rmax = 80.93, 13.09 µM/mg protein, 25.93 μg/mg of protein, 57.84 units/mg protein and 0.08 µM/mg protein, respectively) significantly abolished the respective derangements induced by sodium arsenite. Further, this combination significantly prevented rise in serum cholesterol and triglyceride levels that was induced by sodium arsenite. However, the ameliorative effects of this combination were abated by N-omega-nitro-L-arginine methyl ester (L-NAME) and glibenclamide.
Combined therapy of Telmisartan and omega 3-fatty acids attenuated VED, by activating enzyme nitric oxide synthase (eNOS) through opening of ATP-sensitive K(+) channels.
有效的饮食/药物组合在降低内皮危险因素方面相对于单一疗法可能显示出相加或协同作用。本研究评估了替米沙坦与ω-3脂肪酸联合治疗对亚砷酸钠诱导的大鼠血管内皮功能障碍（VED）的影响。
将48只雄性Wistar大鼠（180 - 220克）随机分为八组；对照组、暴露于亚砷酸钠（1.5毫克/千克/天）组、亚砷酸钠暴露后接受替米沙坦、ω-3脂肪酸、联合用药和/或内皮调节剂治疗2周的组，具体分组取决于分配情况。通过评估血管反应性来评估VED。还测定了血清硫代巴比妥酸反应性物质（TBARS）、亚硝酸盐/硝酸盐水平、还原型谷胱甘肽（GSH）水平、超氧化物歧化酶（SOD）活性、血清胆固醇和甘油三酯水平。
与对照组相比，亚砷酸钠通过减弱乙酰胆碱诱导的内皮舒张（最大舒张率%Rmax = 45.36）、降低血清亚硝酸盐/硝酸盐水平（9.28微摩尔/毫克蛋白）、GSH水平（16.06微克/毫克蛋白）、SOD活性（30.69单位/毫克蛋白）以及增加TBARS（0.19微摩尔/毫克蛋白），从而导致VED。替米沙坦（10毫克/千克/天）与ω-3脂肪酸（180毫克/千克/天）联合治疗（最大舒张率%Rmax分别为80.93、血清亚硝酸盐/硝酸盐水平为13.09微摩尔/毫克蛋白、GSH水平为25.93微克/毫克蛋白、SOD活性为57.84单位/毫克蛋白、TBARS为0.08微摩尔/毫克蛋白）显著消除了亚砷酸钠诱导的相应紊乱。此外，该联合用药显著预防了亚砷酸钠诱导的血清胆固醇和甘油三酯水平升高。然而，N-ω-硝基-L-精氨酸甲酯（L-NAME）和格列本脲减弱了该联合用药的改善作用。
替米沙坦与ω-3脂肪酸联合治疗通过打开ATP敏感性钾（K(+)）通道激活一氧化氮合酶（eNOS），从而减轻VED。
