【摘要】 目的　探讨特异性血管紧张素Ⅱ受体 1阻断剂氯沙坦调节高血压血管内皮功能与一氧化氮合酶 (nitricoxidesynthase,NOS)的关系。 方法　采用两肾一夹型高血压大鼠(two kedney ,one cliphypertensiverat)为动物模型 ,术后第 2、 4、 6wk测血压 ,6wk后处死大鼠测血浆中NO2 -/NO3 -的含量 ,取胸主动脉作离体血管环张力实验 ,免疫印迹方法检测主动脉内皮型一氧化氮合酶 (endothelialNOS ,eNOS)及诱生型一氧化氮合酶 (inducibleNOS ,iNOS)的表达。结果　模型组大鼠相对于假手术对照组血压由 (15 83± 1 4 6 )kPa升高到 (2 3 6 7± 2 2 6 )kPa ,血浆中NO2 -/NO3 -的含量增加 (10 0 8μmol·L-1vs 37 7μmol·L-1,P <0 0 1) ,乙酰胆碱引起的最大舒张百分比下降 (73 5 %vs2 5 % ,P <0 0 1) ,主动脉中eNOS的表达降低 ,iNOS的表达增强 ;氯沙坦治疗后 ,血压、血浆中NO2 -/NO3 -的含量分别下降到 (17 5 6± 1 19)kPa、4 9 1μmol·L-1(P均 <0 0 1) ,乙酰胆碱引起的最大舒张百分比增加到 6 4 2 % ,改善主动脉中eNOS及iNOS的异常表达。结论　氯沙坦可改善两肾一夹型高血压大鼠的血管内皮功能 ,这种作用可能是通过NOS/NO途径调节的更多还原

【Abstract】 AIM To investigate the effects and mechanisms of losartan, a specific blocker of angiotensinⅡ(Ang Ⅱ) receptor (AT 1R), on endothelial dysfunction in two kedney,one clip hypertensive rats. METHODS The levels of blood pressure and plasma NOx were determined. Acetylcholine(ACh) induced vasodilation was measured in rat thoracic aorta. Western blot was performed to valuate the eNOS and iNOS expression of aorta. RESULT The levels of BP and plasma NOx in hypertension group were significantly higher than those of control group.Treatment with losartan(20 mg·kg -1 ·d -1 ) decreased obviously SBP. ACh induced vasodilation was decreased compared with that in control group(73 5% vs 25%, P <0 01). Losartan improved the vasodilation response of aorta to ACh. Compared with control group, the expression of eNOS in hypertension group was decreased, and the level of iNOS was overexpressed. The expression of eNOS and iNOS was normalized by losartan. CONCLUSION Losartan could ameliorate vascular endothelial dysfunction by promoting eNOS and inhibiting iNOS protein expression in two kedney,one clip hypertensive rats.更多还原