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.kg-1.d-1 [SHRcap, number (n) = 43] orally in mixture with milk powder as vehicle from intrautero period of 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.