Reciprocal feedback regulation of kidney angiotensinogen and renin mRNA expressions by angiotensin II.
The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 100, 300, and 1,000 ng.kg-1 x min-1, n = 8/group), significantly increasing mean plasma ANG II concentrations and raising mean arterial blood pressure (MAP). ANG II dose dependently suppressed plasma renin concentration, kidney renin concentration, and renal renin mRNA levels. In contrast, ANG II infusion increased renal angiotensinogen mRNA levels stepwise to 122, 136 (P < 0.05), and 150% (P < 0.05) of control and also increased both liver mRNA levels (P < 0.05) and plasma angiotensinogen concentration (P < 0.05). Three days of angiotensin-converting enzyme inhibition (10 mg.kg-1 x day-1 quinapril in drinking water, n = 8) significantly decreased MAP (P < 0.05) and increased both mean plasma renin concentration (P < 0.05) and renal renin mRNA levels (P < 0.005). Plasma ANG II concentration tended to decrease (not significant), and neither renal nor hepatic angiotensinogen mRNA levels displayed significant difference. However, when data from ANG II-infused and quinapril-treated rats were analyzed together, correlation between plasma ANG II concentrations and renal angiotensinogen mRNA levels was highly significant (P < 0.005, r = 0.585). Thus plasma ANG II upregulates renal angiotensinogen gene expression and downregulates renal renin gene expression, a reciprocal feedback regulation that may have important physiological consequences.
Schunkert
H
H
Cardiovascular Research Center, Stanford University School of Medicine, California 94305-5246.
Ingelfinger
J R
JR
Jacob
H
H
Jackson
B
B
Bouyounes
B
B
Dzau
V J
VJ
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005246:Feedback; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000235:genetics* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin