摘要
目的 :探讨一氧化氮 (NO)缺乏所致高血压、心血管重构的作用及机理。方法 :Wistar大鼠 ,经饮水给予不同药物 ,如下分组 :对照组 (C组 ) :仅给予饮水 ;NO合酶抑制剂组 (L组 ) :L NAME 5 0mg/kg·d-1;大剂量培哚普利组 (L +HA组 ) :L NAME 5 0mg/kg·d-1+培哚普利 4mg/kg·d-1;小剂量培哚普利组 (L +LA组 ) :L NAME 5 0mg/kg·d-1+培哚普利 0 4mg/kg·d-1。每两周监测血压一次 (尾袖法 )。 8周后 ,颈动脉插管测定动脉压、采血样、摘取心脏 ,测定心脏湿重及室壁厚度 ,用病理及体视学方法测定心肌细胞大小、血管中膜厚度、血管周围纤维化程度、管壁厚度 /腔径比、管壁面积 /腔径等心血管重构指标。测定血浆及组织中NO、内皮素 1(ET 1)、血管紧张素AngⅠ、AngⅡ、血管紧张素转换酶 (ACE)含量或活性。结果 :L组大鼠血压明显升高、心血管系统出现明显重构改变 ,血浆中NO含量降低 ,ET、AngI含量增高 ;心肌组织中NO含量降低 ,ACE活性、AngⅡ、AngⅠ含量增高。经大剂量培哚普利 (4mg/kg·d-1)干预后 ,血压得到控制 ,心血管重构及血液、心肌中的生化指标得到改善 ,与对照组相比无明显差异。小剂量培哚普利 (0 4mg/kg·d-1)对血压无明显影响 ,但心室重构得到一定程度的改善。结论 :本研究证实 ,抑制NO合成可引起?
s: Objective: To investigate the mechanisms of nitric oxide deficiency induced by chronic administration of L NAME on hypertension and cardiovascular remodeling. Methods:Male normotensive Wistar Kyoto rats ( n= 32) were divided into four groups and given different drugs via drinking water for 8 weeks. Group C( n= 10): received only tap water; group L ( n= 10): L NAME 50 mg/kg·d -1 ; group L+HA ( n= 6): L NAME 50 mg/kg·d -1 +peridopril 4 mg/kg·d -1 ; group L+LA ( n= 6): L NAME 50 mg/kg·d -1 + peridopril 0 4 mg/kg·d -1 . Tail cuff blood pressure (BP) was measured every two weeks. After 8 weeks, arterial pressure measurement and blood collection through carotid artery were performed. Than,the hearts were removed,weight measured; the ratio of left ventricular mass(LVM) to the body weigh and mean left ventricular wall thickness (LVWT) were determined. Pathologic and stereologic measurements were carried out to determine: the diameter of cardiac myocyte; the lumen(R) and wall area(WA) of small artery; WA/R ratio; and the degree of vascular fibrosis. Myocardial and plasma NO、ET、AngⅠ、AngⅡ、ACE. Results:Group L had higher systolic blood pressure, LVM/BM and mean LVMT,which proved the development of the left ventricular hypertrophy(LVH). The concentrations of NO in myocardium and plasma were lower, but ET 1, AngⅠ were higher in group L than in other groups. The activity of ACE was higher in myocardium but lower in plasma in group L than that in other groups. High dose(4 mg/kg·d -1 ) reduced the BP and improved the process of cardiovascular remodeling(CR), lower doses of peridopril(0 4 mg/kg·d -1 ) improve the degree of CR as well even the BP remained unchanged. Conclusions:The study confirmed that inhibiting NO production lead to hypertension and cardiovascular remodeling. Angiotensin converting enzyme inhibitor(ACEI) could improve CR, which proved that the renin angiotensin system(RAS) in myocardial tissue involoved in cardiovascular remodeling caused by NO deficient.
出处
《高血压杂志》
CSCD
2000年第4期349-354,共6页
Chinese Journal of Hypertension
基金
福建省自然科学基金资助项目
