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Increased adrenal renin in transgenic hypertensive rats, TGR(mREN2)27, and its regulation by cAMP, angiotensin II and calcium

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Item Type:Article
Title:Increased adrenal renin in transgenic hypertensive rats, TGR(mREN2)27, and its regulation by cAMP, angiotensin II and calcium
Creators Name:Peters, J. and Muenter, K. and Bader, M. and Hackenthal, E. and Mullins, J.J. and Ganten, D.
Abstract:The newly established rat strain TGR(mREN2)27 is a monogenetic model in hypertension research. Microinjecting the mouse Ren-2d renin gene caused it to become a stable part of the genome. The rats are characterized by fulminant hypertension, low plasma active renin, suppressed kidney renin, high plasma inactive renin, and high extrarenal transgene expression, most prominently in the adrenal cortex. Additionally, they exhibit significantly enhanced excretion of corticosteroids. Here we demonstrate that part of the plasma renin and most of the adrenal renin are transgene determined and that the adrenal renin is strongly activated. TGR(mREN2)27 adrenal cells may serve as a new tool to investigate the regulation and processing of Ren-2d-derived renin and its significance in hypertension and steroid metabolism. Adrenal renin in TGR(mREN2)27 is stimulated by 8-bromo-cAMP (8-Br-cAMP), angiotensin II (ANGII), and calcium. 8-Br-cAMP significantly stimulates active renin and prorenin release, as well as Ren-2d mRNA. Interestingly, within 60 min 8-Br-cAMP, ANGII, and calcimycin stimulate active renin, but not prorenin release. This indicates different intracellular pathways. An activated adrenal renin-angiotensin system in TGR (mREN2)27 as well as the lack of negative feedback on renin secretion by ANGII may be of pathophysiological significance in this hypertensive model.
Keywords:8-Bromo Cyclic Adenosine Monophosphate, Adrenal Glands, Angiotensin II, Genetically Modified Animals, Calcimycin, Calcium, Cyclic AMP, Animal Disease Models, Enzyme Precursors, Hypertension, Messenger RNA, Sprague-Dawley Rats, Renin, Animals, Mice, Rats
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Volume:91
Number:3
Page Range:742-747
Date:March 1993
Official Publication:https://doi.org/10.1172/JCI116292
PubMed:View item in PubMed

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