Expression of components of the RAS during prolonged blockade at different levels in primates.
To assess the effects of inhibition of the renin-angiotensin system at different levels on plasma concentrations of components of the system and on renin and angiotensinogen gene expression, marmosets on a low-sodium diet were treated for 1 wk by continuous intraperitoneal infusion with either the renin inhibitor CGP-29287, the ACE inhibitor benazeprilat, the angiotensin II antagonist valsartan, the renin inhibitory monoclonal antibody R-3-36-16, or vehicle. Plasma total immunoreactive renin increased (14- to 20-fold) after all three modes of interference. Plasma angiotensinogen was significantly reduced in the benazeprilat- and valsartan-treated marmosets but not in the CGP-29287-treated animals. Plasma concentration of angiotensin II was significantly decreased in the benazeprilat-, CGP-29287-, and R-3-36-16-treated marmosets and was increased in the valsartan-treated marmosets. Kidney renin mRNA level increased 8- to 15-fold in all groups. Hepatic angiotensinogen mRNA level increased with CGP-29287 treatment but decreased with the other treatments. Kidney angiotensinogen mRNA level was not affected by any treatment. Different modes of inhibition of the renin-angiotensin system have different effects on plasma components of the system and liver angiotensinogen expression.
Samani
N J
NJ
Department of Medicine, University of Leicester, United Kingdom.
Cumin
F
F
Kelly
M
M
Wood
J M
JM
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002144:Callithrix / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D000092502:Renin Inhibitors
D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000808:Angiotensinogen; D000911:Antibodies, Monoclonal; D001552:Benzazepines; D009842:Oligopeptides; D012333:RNA, Messenger; D012083:Renin; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000092502:Renin Inhibitors; C045501:CGP 29287; C052133:benazeprilat