缬沙坦对腹主动脉缩窄大鼠心血管重构的影响

Effects of valsartan on cardiovascular remodeling in rats with abdominal aorta coarctation

目的观察血管紧张素Ⅱ1型受体拮抗剂缬沙坦对腹主动脉缩窄(AAC)大鼠心血管重构的影响。方法用AAC法建立动物模型,将32只雄性SD大鼠随机分成4组:假手术组,AAC对照组,AAC低剂量缬沙坦组(1mg·kg-1·d-1),AAC高剂量缬沙坦组(30mg·kg-1·d-1),每组8只。药物经灌胃6周后通过颈动脉测定收缩压,同时测定左心室重量指数。用图像分析仪检测出主动脉和肠系膜上动脉中膜厚度/管腔内径比值。用放射免疫法测定血浆及心血管中的血管紧张素Ⅱ、醛固酮。结果无显著降压作用的低剂量缬沙坦能抑制主动脉、肠系膜上动脉中膜肥厚及左心室肥厚,但明显降低血压的高剂量作用更显著,AAC高剂量缬沙坦组上述各项参数与假手术组无显著性差异。结论缬沙坦能抑制AAC大鼠心血管重构,其可能机制是与抑制了心血管局部肾素-血管紧张素-醛固酮系统的活性有关。

Objective To investigate the effects of valsartan on cardiovascular remodeling in rats with abdominal aorta coarctation（AAC）. Methods The model of animal was established by using the method of abdominal aortic coarctation. Thirty-two male SD rats were randomly divided into 4 groups ： sham-operated rots serving as controls ; AAC rats serving as controls ; AAC rats receiving low-dose valsartan treatment, 1 mg·kg^- 1· d^- 1 and AAC rots receiving high-dose valsartan treatment, 30 mg·kg^-1·d^-1 . The drug was administered by gavage for 6 weeks. At the end of the treatment, systolic pressure was measured via catheter in the carotid artery. The heart was taken and weighed to calculate the left ventricular weight index（LVMI）. The ratio of mean thickness of media to mean diameter of lumen of aorta and superior mesenteric artery was calculated by morphometry. Concentrations of angiotensin Ⅱ and aldosterone in plasma and in cardiovascular tissue were determined by radioimmunoassay. Results There was no significant difference in carotid systolic pressure between AAC group and low-dose valsartan group, but low-dose valsartan might inhibit hypertrophy of left ventricle and hypertrophy of the tunica media of aorta and superior mesenteric artery. High-dose valsartan group was more effective compared with sham-operated group. All parameters had no significant difference between high-dose valsartan group and sham-operated group. Conclusion Valsartan is effective in suppressing cardiovascular remodeling in the AAC rots. The above effects of valsartan may be explained by inhibition of tissue rennin-angiotensin system in both heart and vascular wall and increaseing circulating Ang Ⅱ level.