title: Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The long-term inhibition of tissue RAS is one of the mechanisms of the persistent hypotensive effect of captopril treatment.
authors.affiliation: Hypertension Division, First Affiliated Hospital, Fujian Medical College, Fuzhou, China.
authors.forename: W Y
authors.initials: WY
authors.lastname: Hu
authors.forename: D G
authors.initials: DG
authors.lastname: Chen
authors.forename: S C
authors.initials: SC
authors.lastname: Chen
authors.forename: X Q
authors.initials: XQ
authors.lastname: Jin
authors.forename: H J
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000808:Angiotensinogen / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D002216:Captopril; D007703:Peptidyl-Dipeptidase A