【摘要】 卡托普利长期治疗自发性高血压大鼠对循环和局部肾素血管紧张素系统的影响１胡文养２，陈达光，陈松苍，晋学庆，王华军（福建医学院附属第一医院高血压研究室，福州３５０００５，中国）关键词肽基二肽酶Ａ；高血压；左心室肥大；卡托普利；近交系ＳＨＲ大鼠；ＲＮＡ...更多还原

【Abstract】 IM: To study the effect of captopril treatment and its withdrawal on the circulating and tissue peptidyl dipeptidase A, angiotensinogen (AGT), and angiotensin Ⅱ ( AⅡ ), in relation to left ventricular hypertrophy (LVH) and systolic blood pressure (SBP). METHODS: SHR ♂ rats were given captopril 100 mg·kg -1 ·d -1 [SHR cap , number ( n )=43] orally in mixture with milk powder as vehicle from intrautero period to 16 wk of age. Rats were killed at 16 ( n =19) and 40 ( n =24) wk of age, respectively. Male, age matched untreated SHR and WKY rats served as controls. SBP, left ventricular mass/body weight (LVM/BW) ratio, left ventricular (LV) myocardium and plasma AⅡ concentration, aortic and serum peptidyl dipeptidase A activity, AGT mRNA level in kidney and liver, renal renin mRNA level were determined. RESULTS: Captopril treatment decreased SBP and reduced LVM/BW at 16 and 40 wk of age, and persistently inhibited LV myocardium AⅡ , aortic peptidyl dipeptidase A activity, and AGT gene expression in kidney even after the treatment was removed. Nevertheless, no changes were found in plasma AⅡ concentration, serum peptidyl dipeptidase A activity, and AGT mRNA level in liver by captopril therapy. Renal renin mRNA level was low in SHR and WKY rats, but it was increased by captopril treatment. Tissue renin angiotensin system (RAS) such as AGT mRNA in kidney, aortic peptidyl dipeptidase A activity, and LV myocardium AⅡ , rather than circulating RAS (AGT mRNA in liver, renin mRNA in kidney, serum peptidyl dipeptidase A activity and plasma AⅡ ), were persistently inhibited by early captopril treatment, even after the withdrawal of the treatment. CONCLUSION: The long term inhibition of tissue RAS is one of the mechanisms of the persistent hypotensive effect of captopril treatment.更多还原