Peripheral and central angiotensin II regulates expression of genes of the renin-angiotensin system.
We investigated whether angiotensin (ANG) II has the potential to regulate expression of genes of the renin-angiotensin system (RAS) in peripheral and central tissues. ANG II (0.1 or 6.0 nmol/h) was infused by osmotic minipump into male Sprague-Dawley rats (225-250 g) for 5 days, either intravenously or intracerebroventricularly. We measured angiotensinogen mRNA in liver, adrenal glands, and brain (hypothalamus and lower brain stem), renin mRNA in the kidney, and angiotensin-converting enzyme (ACE) mRNA in the lung and testis by Northern blot analysis. We demonstrated that plasma ANG II increases the levels of liver angiotensinogen mRNA, decreases kidney renin mRNA, and decreases lung ACE mRNA. Intracerebroventricular administration of ANG II resulted in a different pattern of responses of the peripheral RAS components. Liver angiotensinogen mRNA was increased, and kidney renin mRNA was decreased by both doses of ANG II, whereas lung ACE mRNA remained unresponsive at either dose. Centrally mediated influences of ANG II are most likely indirect since plasma ANG II concentration was not changed. This study has revealed that ANG II has profound diverse effects that influence the regulation of its formation. Further, results indicate that genes of the RAS responded to exogenous ANG II in both tissue- and route-specific ways.
Kohara
K
K
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195.
Brosnihan
K B
KB
Ferrario
C M
CM
Milsted
A
A
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008099:Liver / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000235:genetics*; D014018:Tissue Distribution
D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin