黄连碱对L-NAME诱导高血压大鼠胸主动脉功能的影响

Effect of coptisine on the function of isolated thoracic aorta of L-NAME induced hypertensive rats

目的探讨黄连碱对L-NAME致高血压大鼠胸主动脉舒缩功能的影响。方法采用NO合酶抑制剂L-NAME制备大鼠高血压模型,然后每天灌胃给予黄连碱低(10 mg.kg-1)、中(30 mg.kg-1)、高(100 mg.kg-1)3个剂量;给药干预6周后采用体外血管环活性评价方法,评价各组大鼠胸主动脉的收缩和舒张功能。结果 L-NAME诱导大鼠高血压模型,其胸主动脉的收缩和舒张功能均受到影响。给予黄连碱6周,黄连碱可明显增强L-NAME诱导高血压大鼠血管平滑肌对细胞内钙释放引起的收缩反应,并降低外钙内流引起的血管收缩能力,但对大鼠血压无影响,对血管的收缩功能和内皮依赖的舒张功能影响不大。结论 L-NAME制备大鼠高血压模型主要与NO的减少有关,而黄连碱可能影响IP3-Ca2+通路,对L-NAME诱导大鼠高血压没有降压作用。

Aim To investigate the effect of coptisine on the vascular activity of hypertensive rats treated by L-NAME.Methods Coptisine was orally administered for 6 weeks after the hypertension was established by L-NAME treatment in rats.Then the rat aorta was harvested to evaluate its vasoactivity induced by various stimulus.Results Chronic inhibition of nitric oxide synthesis by L-NAME led to sustained elevation of blood pressure of rats,as well as vascular dysfunction.Coptisine failed to block the increase of systolic blood pressure in the L-NAME treated rats without affecting the vasocontrictory profile and the endothelium-dependent vasorelaxation.However,the contraction induced by intracellular Ca^2＋ released by the sarcoplasmic reticulum was enhanced by coptisine treatment,whereas the contractile response to CaCl2 in Ca^2＋-free medium was decreased due to coptisine therapy.Conclusions These results indicate that the hypertension induced by L-NAME is associated with NO deficiency and coptisine might interfere with the IP3-Ca^2＋ pathway in rat aortas.Coptisine shows no antihypertensive action on the L-NAME induced hypertensive rats.