Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats.
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.
Hu
W Y
WY
Hypertension Division, First Affiliated Hospital, Fujian Medical College, Fuzhou, China.
Chen
D G
DG
Chen
S C
SC
Jin
X Q
XQ
Wang
H J
HJ
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*
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D002216:Captopril; D007703:Peptidyl-Dipeptidase A