Discrepancy between renin mRNA and plasma renin level in angiotensin-converting enzyme inhibitor-treated rats.
1. To investigate the role of transcriptional and post-transcriptional factors in increasing renin synthesis secondary to angiotensin-converting enzyme (ACE) inhibitors, we studied the changes in levels of renal renin mRNA, plasma renin and other hormonal factors. 2. Spontaneously hypertensive rats were orally administered 10 mg/kg spirapril or vehicle daily for 3, 14 or 28 days. 3. Plasma renin activity in the spirapril-treated group was significantly elevated compared with that in the vehicle group at any time (P < 0.01). However, there was no significant change in plasma angiotensin II concentration between the two groups. The ratio of renal renin mRNA to beta-actin mRNA in the spirapril-treated group was higher than that in the control group (P < 0.01). 4. At 28 days, plasma renin activity in the spirapril-treated group was significantly elevated compared with that at 14 days (P < 0.05). However, there was no change in renin mRNA between 14 and 28 days after ACE inhibitor administration. 5. Plasma ACE activity in the treatment group was less than that in the control group at any time (P < 0.01). 6. Our study demonstrated a non-proportional change in plasma renin and renal renin mRNA levels. It is suggested that the main determinant of the rate of renin synthesis after administration of an ACE inhibitor may be post-transcriptional factors, and that unknown mechanisms may be involved in the increase in plasma renin level after long-term administration of ACE inhibitor in addition to the short feedback mechanism brought about by the decrease in angiotensin II.
Department of Geriatric Medicine, Osaka University Medical School, Japan.
R
R
Morishita
J
J
Higaki
M
M
Nagano
F
F
Nakamura
N
N
Tomita
Y
Y
Zhao
H
H
Mikami
M
M
Miyazaki
T
T
Ogihara
D000199:Actins / Q000235:genetics; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; C052555:spirapril; D007703:Peptidyl-Dipeptidase A; D012083:Renin