Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats
Hu, W.Y.; Chen, D.G.; Chen, S.C.; Jin, X.Q.; Wang, H.J.
Zhongguo Yao Li Xue Bao 17(6): 507-512
1996
ISSN/ISBN: 0253-9756 PMID: 9863143 Document Number: 457090
AIM: To study the effect of captopril treatment and its withdrawal on the circulating and tissue peptidyl-dipeptidase A, angiotensinogen (AGT), and angiotensin II (A II) , in relation to left ventricular hypertrophy (LVH) and systolic blood pressure (SBP). METHODS: SHR male rats were given captopril 100 mg cntdot kg-1 cntdot 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 A II 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 A II , aortic peptidyl-dipeptidase A activity, and AGT gene expression in kidney even after the treatment was removed. Nevertheless, no changes were found in plasma A II 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 A II, rather than circulating RAS (AGT mRNA in liver, renin mRNA in kidney, serum peptidyl-dipeptidase A activity and plasma A II), 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.