缬沙坦对自发性高血压大鼠血管结构和舒缩功能的影响

Effects of valsartan on the structure and function of vessels in spontaneously h ypertensive rats

目的 :观察缬沙坦对自发性高血压大鼠(SHR)的血压、血管功能和结构的影响。方法 :30只12wk龄雄性SHR ,随机分成 3组 ,每组 10只 :缬沙坦大剂量组 (30mg·kg-1·d-1) ;缬沙坦小剂量组(10mg·kg-1·d-1) ;SHR模型对照组 ,另设同龄雄性正常血压WKY大鼠作为正常对照组 (n =10 )。用无创法测定尾动脉收缩压及心率 ,至给药 4wk处死。测定胸主动脉、肠系膜动脉分支第三级血管壁(中膜 ) 腔面积比 ,并采用平衡记录仪记录离体的动脉环对血管活性药物去甲肾上腺素 (NE)和硝普钠反应的敏感性。结果 :与模型组相比 ,大、小剂量缬沙坦均能降低SHR血压 ,肠系膜动脉壁肥厚明显改善 (P <0 .0 1) ;大剂量明显减少主动脉腔壁比 (P <0 .0 1) ,小剂量缬沙坦也可减少腔壁比 ,但无统计学意义 ;大、小剂量均能使胸主动脉及肠系膜动脉对硝普钠的舒张敏感性增加 (P <0 .0 5 ) ,对NE收缩的敏感性降低 (P <0 .0 5 )。结论 :缬沙坦能改善SHR的非内皮依赖性血管舒张功能 ,使SHR血管对循环〗活性物质的异常反应改善 ,并抑制SHR的血管壁变厚。

AIM: To evaluate the effects of valsartan on the structure an d function of vessels in spontaneously hypertensive rats (SHR). METHODS : 30 twelve-week-old male SHRs were divided into three groups at rando m:untreated control (n=10), low-dose valsartan (10 mg·kg -1 ·d -1 , n=10),and high-dose Valsartan (30 mg·k g -1 ·d -1 , n=10). Valsartan was given by gavage for 4 weeks, while SHR control and 10 age- and sex-matched Wistar Kyoto rats (WKY ) were given water only. Systolic blood pressure (SBP) was measured using tail- cuff technique. Wall to lumen area ratios (W/L) of thoracic aorta and mesenteric artery (3rd grade branch) were assessed by morphormetic assay. The effect of va lsartan on the vascular reactivity o the vasoactive substance: norepinephrine an d sodium nitroprusside were studied by using rings of thoracic aorta and mesente ric arteries isolated from rats. RESULTS: After 4-week treatmen t, the levels of SBP in both high and low-dose groups were significantly lower than those in control group (P< 0.05 ). The values of W/L of m esenteric artery in the two treatment groups were markedly reduced than those in the control group (P< 0.05 ), and the values of W/L of thorac ic aorta in the high -dose group were markedly reduced than those in the contro l group (P< 0.01 ). Both mesenteric artery and thoracic aorta in valsartan treated groups exhibited significantly depressed function of vasoco nstriction response to noradrenaline and enhanced function of vasodilation to SN P. CONCLUSION: Valsartan can meliorate the function of resistant vessels by enhancing their sensitivity to vasodilator and depressing the sensit ivity to vasoconstrictor; and also attenuate the resistant vascular hypertrophy during the development of hypertension in SHR.