吲哒帕胺和牛磺酸联用的降压作用及机制研究

Antihypertensive effects and mechanism of indapamide and taurine in combination

目的考察吲哒帕胺(Indapamide,Ind)和牛磺酸(Taurine,Tau)联用对自发性和肾性高血压大鼠的降压作用并对机制进行初步探讨。方法采用自发性高血压大鼠,通过2因素3水平正交试验,考察Ind与Tau联用的最佳配伍剂量;采用自发性和肾性高血压大鼠,连续ig给药7和14 d,观察给药前后血压变化;采用离体大鼠胸主动脉环,考察Ind和Tau对由去甲肾上腺素预收缩动脉环的舒张作用;采用人脐静脉内皮细胞(HUVECs),考察Ind和Tau对磷酸化一氧化氮合酶(pe NOS)表达的影响。结果 Ind与Tau联用的最佳剂量配伍为0. 25 mg·kg-1+100 mg·kg-1; Ind和Tau单用和联用均能明显降低自发性和肾性高血压大鼠的血压,且联合用药的降压作用优于单药;Ind和Tau单用和联用对去甲肾上腺素预收缩大鼠胸主动脉环有舒张作用,且两药联用具有协同作用; Ind和Tau能增加HUVECs中p-e NOS的表达。结论 Ind和Tau联用能降低自发性和肾性高血压大鼠的血压,其作用机制与舒张血管、增加血管内皮p-e NOS的表达相关,且两药联用具有协同作用。

Objective To observe the antihypertensive effects of indapamide( Ind) and taurine( Tau) in combination on spontaneous hypertensive rats( SHR) and renal hypertensive rats( RHR),and to investigate the mechanism. Methods The best combination dose of Ind and Tau was studied on SHR by the orthogonal test of 2 factors and 3 levels;The SHR and RHR were administered ig with Ind and Tau for 7 or 14 days,and the antihypertensive effects were investigated;The vasodilation effects of Ind and Tau were studied on rat aortic ring preparations precontracted with norepinephrine( NE);The effects of Ind and Tau on endothelial nitric oxide synthase( eNOS) and p-eNOS in HUVECs were determined by western blotting. Results The best combination dose of Ind and Tau was 0. 25 mg·kg-1+ 100 mg·kg-1;After administration,the blood pressure of rats in Ind group,Tau group,Ind-Tau group were decreased significantly. The effects of Ind-Tau groups were better than the Ind group and the Tau group;Ind,Tau or Ind-Tau produced relaxation effects on NE-induced rat thoracic aortic ring contraction. Ind-Tau had shown the synergetic effect;the p-eNOS levels were increased by Ind or Tau treatment in HUVECs. Conclusion The use of Ind and Tau alone or in combination can lower the blood pressure of hypertensive rats;Ind and Tau alone or in combination can dilate blood vessels in vitro and increase the p-eNOS level in HUVECs. Combination treatment is better than any single agent alone in functional assays.